- Email: [email protected]
168. Assembly of Chimeric Antigen Receptor Targeting αVβ6-Expressing Pancreatic Cancer
CANCER-IMMUNOTHERAPY I CNA12-CTLs persisted longer, homed to the tumour and expanded more than eGFP-CTLs in mice treated with FK506 (P<0.0001). Mice receiving CNA12-CTLs and treated with FK506 survived significantly longer (P<0.0001) than control treated animals. Our results demonstrate that CNA12-CTL induce regression of EBVassociated tumours in vivo despite ongoing immunosuppression. Clinical application of this novel approach may enhance the efficacy of adoptive transfer of EBV-CTL in SOT patients developing PTLD without the need for reduction in immunosuppressive therapy. We are now planning a clinical study based on a “double marking” approach, comparing the survival and expansion of autologous CNA12CTLs and control retroviral vectors. We will generate 2 retroviral vectors encoding (a) Q8 alone (12 residue epitope from CD34 attached to the stalk and transmembrane regions of CD8) as marker gene (b) a bicistronic vector co-expressing CNA12 with Q8 using the self-cleaving 2A sequence (which allows the two genes of interest to be transcripted simultaneously and then cleaved).
More broadly, this represents a generic approach enabling T-cells derived against other tumours to function in SOT patients on immunosuppression.
166. Production of T Cells for Adoptive Cellular Immunotherapy Using the XuriTM Cell Expansion System W25
Ray A. Ismail,1 Sarah M. Stone,1 Angela S. Marenghi,1 Tamara O. Fedczyna,2 William D. Shingleton.1 1 Cell BioProcess, GE Healthcare, Cardiff, United Kingdom; 2Cell BioProcess, GE Healthcare, Piscataway, NJ.
Immunotherapeutic products can be classified broadly into (1) active immunotherapy (therapeutic vaccines), (2) adoptive cellular immunotherapy (transfer of immune cells, genetically modified T-cells or precursor cells) or (3) passive immunotherapy (antibody or receptor ligand administration). Adoptive cellular immunotherapy products are the most recent to show signs of benefit and therapeutic value to the patient population, and there is now an emerging need to develop more effective manufacturing processes that will require less user intervention, permit scale-out, minimise the risk of cell contamination, achieve high cell densities, allow careful control of the expansion protocol and be suited for a regulated environment. The Xuri™ Cell Expansion System W25, based on the well-known WAVETM rocking technology, offers many advantages in this regard over the commonly used static systems. Xuri W25 is a functionally closed, single use bioreactor for working volumes between 0.3 and 25L, which is suitable for use in a regulated environment and offers comprehensive process monitoring and remote control capabilities. Data presented here compares the performance of Xuri W25 to commonly used static bioreactors with regard to workflows, cell yield, cellular phenotype, functional performance, cost and risk. The expanded T cells remain biologically functional and can be reactivated post expansion to produce high amounts of cytokines. The cytokine expression profile confirms the presence of TH1 phenotype, naïve/early phenotype and low in senescence markers. This data demonstrates that Xuri W25 is capable of expanding functional T-cells for therapy in a safer, low risk and more cost effective way compared to the static systems used in this study. Molecular Therapy Volume 22, Supplement 1, May 2014 Copyright © The American Society of Gene & Cell Therapy
167. A Modular Extracellular Sensor Architecture (MESA) for Engineering Mammalian Cell-Based Therapies to Interface with Human Physiology
Joshua N. Leonard.1 Chemical and Biological Engineering, Northwestern University, Evanston, IL. 1
The ability to engineer customized mammalian cellular functions would enable the construction of sophisticated cell-based therapeutics and transformative tools for fundamental biological research. Such capabilities could overcome persistent barriers to treatment in applications ranging from cancer immunotherapy to regenerative medicine. The emerging field of synthetic biology provides such an approach for building novel cellular functions, and the “toolbox” of biological parts that operate in mammalian cells is rapidly expanding. To date, however, we lack the ability to construct synthetic cellbased biosensors that detect and respond to exclusively extracellular cues. Because many species of biological relevance, including cytokines, chemokines, cell-surface antigens, and many pathogens are exclusively extracellular, engineering cell-based devices that interface robustly with host physiology will require sensors for extracellular species. To meet these needs, we have developed a Modular Extracellular Sensor Architecture (MESA). This technology enables the construction of cell surface receptors that transduce the detection of an extracellular ligand into a change in intracellular state (i.e., regulation of a transgene) without utilizing any native signal transduction pathways. Unlike native receptors, these engineered modular receptors are readily customized to respond to novel ligands and to signal through novel engineered transcription factors. Thus, this system is orthogonal to cellular processes and can be integrated into engineered gene circuits. For example, we have multiplexed MESA receptors to construct functions such as combinatorial logical evaluation of external stimuli. Development of MESA technologies and application to immune monitoring and cancer immunotherapy will be discussed.
168. Assembly of Chimeric Antigen Receptor Targeting αVβ6-Expressing Pancreatic Cancer Kendra A. Hyland,1 Erik R. Olson,1 R. Scott McIvor.1 Discovery Genomics, Inc., Minneapolis, MN.
1
Pancreatic cancer represents the 10th most common cancer diagnosis, yet the 4th most common estimated cause of death. The only potential curative therapy for pancreatic cancer is surgical resection; however, few patients have tumors that can be resected. Pancreatic ductal adenocarcinoma, which represents 90% of pancreatic cancers, is particularly aggressive, since it rapidly metastasizes and often expresses growth factors and signaling components that permit rapid growth. Alternative therapies are desperately needed, as there have been no recent medical advances for treatment of pancreatic adenocarcinoma. Immunotherapy by adoptive transfer of engineered T cells can mediate cancer regression and overcome evasive mechanisms by which tumors avoid immune responses. Chimeric antigen receptors (CAR) are engineered fusion molecules comprising an antigen-binding motif and intracellular signaling domains. CAR can recognize tumor antigens independently of major histocompatiblity complex, expression of which is often lost by tumor cells. We assessed the ability of several antigen-binding domains in the context of CAR to bind αVb6, an integrin that is highly expressed on pancreatic cancer cells. A CAR incorporating a peptide from foot-and-mouth disease virus VP1 capsid protein, a human IgG Fc spacer region, a transmembrane spanning domain and a fusion of intracellular signaling domains from CD28 and CD3z provided the highest level of binding to αVb6. Primary T-cells were then engineered for CAR expression using the Sleeping Beauty transposon system. S63
CANCER-IMMUNOTHERAPY I Artificial antigen presenting cells expressing αVb6 integrin protein were engineered for specific expansion of CAR-expressing primary T cells. Functional activation of the assembled CAR in primary T-cells was determined by secretion of IFNg upon exposure of the engineered T cells to either αVb6 protein or αVb6+ pancreatic cancer cells. These results demonstrate the feasibility of assembling CAR to target αVb6 integrin and support anticipated antitumor activity of these cells in preclinical studies and ultimately in the treatment of human pancreatic cancer.
169. Clinically Adaptable CD19-Specific Chimeric Antigen Receptor
Iulia Diaconu,1 Barbara Savoldo,1 Gianpietro Dotti.1 1 Center for Cell and Gene Therapy, Baylor College of Medicine, Houston. Immunotherapy with CAR-redirected T-cells can cure CD19+ leukemias. However, the occurrence of cytokine storms, prolonged B-cell aplasia (> 18 months) and occurrence of Graft-versus-HostDisease (GvHD) when donor CAR-T cells are used after allogeneic hematopoietic stem cell transplant (HSCT) remain drawbacks. To address these limitations, we developed a new vector encoding 3 components: (1) CAR.CD19 including the 4-1BB endodomain; (2) the iCaspase9 (iC9) suicide gene, to eliminate transgenic cells in case of acute toxicity or GvHD, or to specifically terminate prolonged B-cell aplasia “on demand”; (3) the DNGFR marker, to select transgenic T-cells, when infused after allogeneic HSCT. In this study we compared the new iC9-DNGFR-CAR.CD19 (CAR-iC) vector with a vector encoding the same CAR.CD19 (CAR) alone. Transduction efficiency with the new vector was 63%±9% and, after the selection for NGFR, 98%±1% of the cells co-express CAR and DNGFR. Selected T-cells were expanded for 10 days in the presence of IL-7 and IL-15, and then tested for functionality. Both CAR-iC+ and CAR+ T-cells expanded well (median 230-fold and 320-fold, respectively). Cytotoxic activity based on 51Cr release assay, was comparable, with killing of CD19+ tumor targets (Raji) at an E:T ratio of 20:1 of 89%±13% with CAR-iC+ T cells versus 94%±9% with CAR+ T cells. Longer-term antitumor activity, assessed by coculture assays with Raji for 5 days, showed complete elimination of CD19+ tumor cells by both CAR-iC+ and CAR+ T cells at all ratios used. Functionality of the iC9 gene was assessed by exposing CARiC+ T-cells to CID which induced >98% apoptosis after 24 hrs, while control CAR+ T-cells remained unaffected. Finally, we performed experiments in vivo in NSG mice reconstituted with human-cord blood derived CD34+ cells. Upon engraftment of human B cells, HLA mismatched FireFly-Luciferase-labelled CAR-iC+ T-cells (5x106) were infused i.v. and their persistence monitored by IVIS imaging. CAR-iC+ T cells completely eliminated B cells in association with a concomitant expansion of T cells. As B-cell aplasia occurred, CARiC+ T cells subsequently contracted, even if bioluminescent signals remained detectable for >3 months, and T-cells were detectable in peripheral blood, spleen and bone marrow by flow cytometry. At the peak of T-cell expansion, with corresponding B-cell aplasia, a group of mice received one single dose of CID (50μg/mouse). This resulted in a rapid (<48hrs) and significant reduction and disappearance of the bioluminescent signal indicating elimination of circulating T cells, that was confirmed by FACS analysis. Reconstitution of B lymphocytes followed within 2 months. Our data support the advantages of our proposed CAR-iC vector for adoptive T-cell therapy of B-cell malignancies, offering efficient removal of T-cells in both the autologous and allogeneic settings with control of toxicities and termination “on demand” of prolonged and unwanted B-cell aplasia without loss of the antitumor response.
S64
170. Low MHC Class I Expression in Pediatric Malignancies May Impede Success of MHCDependent Immunotherapies
Kellie Haworth,1,2 Michael Arnold,1 Jennifer Leddon,2,3 Chun-Yu Chen,2 Timothy Cripe.1,2 1 Pediatric Hematology/ Oncology/ BMT, Nationwide Children’s Hospital, Columbus, OH; 2Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children’s Hospital, Columbus, OH; 3University of Cincinnati Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinatti, OH. Immunotherapies are gaining considerable traction with increasing reports of antitumor efficacy in some FDA-approved agents. Some strategies are MHC-independent, such as T-cells engineered to express chimeric receptors (CARs) and bi-specific antibodies (BiTEs), but others, such as cancer vaccines, are dependent upon recognition of antigenic peptides presented by major histocompatibility complexes (MHC). There is growing recognition that oncolytic viruses also exert their therapeutic effects in part by inducing an adaptive T-cell response against tumor-associated antigens. Although, the dependence on MHC Class I for the T-cell-dependent effects of oncolytic virotherapy is intuitive, and has not been formally addressed. Unfortunately, tumor cell interaction with the immune system is limited with the loss of tumor antigens, lack of chemokines, lack of adhesion molecules, lack of tumor vascularization, and loss of MHC Class I expression. For those types of immunotherapies which are dependent upon MHC Class I antigen presentation, it is important to know the MHC Class I expression on tumor cells, and, in the case of virotherapy, the effects of infection on MHC Class I expression. In adult cancers, MHC Class I expression has been extensively studied, with down-regulation seen in 40-90% of cases and associated with a poor prognosis. However, few studies have examined MHC Class I expression in pediatric cancers. As oncolytic virotherapy trials have expanded to the pediatric population, we sought to address this paucity of information and determine whether MHC Class I down-regulation may serve as a barrier to virotherapy and other MHC-restricted therapies. We queried mRNA expression microarray databases including clinical and preclinical datasets for MHC Class I expression. Our preliminary data suggest that sarcomas, including Ewing sarcoma, osteosarcoma, and both embryonal and alveolar rhabdomyosarcomas, Wilms’ tumors, and some brain tumors, such as AT/RT (atypical teratoid/ rhabdoid tumors) and ependymomas, also exhibit decreased MHC Class I mRNA levels relative to other cancer types. In some human rhabdomyosarcoma cell lines, we found that MHC Class I can be up-regulated in vitro, indicating a reversible epigenetic mechanism for down-regulation. Preliminary results in immunocompetent murine rhabdomyosarcoma models suggest that the in vivo therapeutic effect of oHSV is largely T-cell dependent and that the best therapeutic response, including complete tumor rejection and resistance to tumor re-challenge, correlated with the highest MHC Class I expression. We therefore believe that the establishment of MHC Class I assays will likely serve as important biomarkers for patient inclusion in therapeutic trials of MHC-dependent immunotherapies, and modulation of MHC Class I expression may be a promising strategy to enhance oncolytic virotherapy.
Molecular Therapy Volume 22, Supplement 1, May 2014 Copyright © The American Society of Gene & Cell Therapy
More broadly, this represents a generic approach enabling T-cells derived against other tumours to function in SOT patients on immunosuppression.
166. Production of T Cells for Adoptive Cellular Immunotherapy Using the XuriTM Cell Expansion System W25
Ray A. Ismail,1 Sarah M. Stone,1 Angela S. Marenghi,1 Tamara O. Fedczyna,2 William D. Shingleton.1 1 Cell BioProcess, GE Healthcare, Cardiff, United Kingdom; 2Cell BioProcess, GE Healthcare, Piscataway, NJ.
Immunotherapeutic products can be classified broadly into (1) active immunotherapy (therapeutic vaccines), (2) adoptive cellular immunotherapy (transfer of immune cells, genetically modified T-cells or precursor cells) or (3) passive immunotherapy (antibody or receptor ligand administration). Adoptive cellular immunotherapy products are the most recent to show signs of benefit and therapeutic value to the patient population, and there is now an emerging need to develop more effective manufacturing processes that will require less user intervention, permit scale-out, minimise the risk of cell contamination, achieve high cell densities, allow careful control of the expansion protocol and be suited for a regulated environment. The Xuri™ Cell Expansion System W25, based on the well-known WAVETM rocking technology, offers many advantages in this regard over the commonly used static systems. Xuri W25 is a functionally closed, single use bioreactor for working volumes between 0.3 and 25L, which is suitable for use in a regulated environment and offers comprehensive process monitoring and remote control capabilities. Data presented here compares the performance of Xuri W25 to commonly used static bioreactors with regard to workflows, cell yield, cellular phenotype, functional performance, cost and risk. The expanded T cells remain biologically functional and can be reactivated post expansion to produce high amounts of cytokines. The cytokine expression profile confirms the presence of TH1 phenotype, naïve/early phenotype and low in senescence markers. This data demonstrates that Xuri W25 is capable of expanding functional T-cells for therapy in a safer, low risk and more cost effective way compared to the static systems used in this study. Molecular Therapy Volume 22, Supplement 1, May 2014 Copyright © The American Society of Gene & Cell Therapy
167. A Modular Extracellular Sensor Architecture (MESA) for Engineering Mammalian Cell-Based Therapies to Interface with Human Physiology
Joshua N. Leonard.1 Chemical and Biological Engineering, Northwestern University, Evanston, IL. 1
The ability to engineer customized mammalian cellular functions would enable the construction of sophisticated cell-based therapeutics and transformative tools for fundamental biological research. Such capabilities could overcome persistent barriers to treatment in applications ranging from cancer immunotherapy to regenerative medicine. The emerging field of synthetic biology provides such an approach for building novel cellular functions, and the “toolbox” of biological parts that operate in mammalian cells is rapidly expanding. To date, however, we lack the ability to construct synthetic cellbased biosensors that detect and respond to exclusively extracellular cues. Because many species of biological relevance, including cytokines, chemokines, cell-surface antigens, and many pathogens are exclusively extracellular, engineering cell-based devices that interface robustly with host physiology will require sensors for extracellular species. To meet these needs, we have developed a Modular Extracellular Sensor Architecture (MESA). This technology enables the construction of cell surface receptors that transduce the detection of an extracellular ligand into a change in intracellular state (i.e., regulation of a transgene) without utilizing any native signal transduction pathways. Unlike native receptors, these engineered modular receptors are readily customized to respond to novel ligands and to signal through novel engineered transcription factors. Thus, this system is orthogonal to cellular processes and can be integrated into engineered gene circuits. For example, we have multiplexed MESA receptors to construct functions such as combinatorial logical evaluation of external stimuli. Development of MESA technologies and application to immune monitoring and cancer immunotherapy will be discussed.
168. Assembly of Chimeric Antigen Receptor Targeting αVβ6-Expressing Pancreatic Cancer Kendra A. Hyland,1 Erik R. Olson,1 R. Scott McIvor.1 Discovery Genomics, Inc., Minneapolis, MN.
1
Pancreatic cancer represents the 10th most common cancer diagnosis, yet the 4th most common estimated cause of death. The only potential curative therapy for pancreatic cancer is surgical resection; however, few patients have tumors that can be resected. Pancreatic ductal adenocarcinoma, which represents 90% of pancreatic cancers, is particularly aggressive, since it rapidly metastasizes and often expresses growth factors and signaling components that permit rapid growth. Alternative therapies are desperately needed, as there have been no recent medical advances for treatment of pancreatic adenocarcinoma. Immunotherapy by adoptive transfer of engineered T cells can mediate cancer regression and overcome evasive mechanisms by which tumors avoid immune responses. Chimeric antigen receptors (CAR) are engineered fusion molecules comprising an antigen-binding motif and intracellular signaling domains. CAR can recognize tumor antigens independently of major histocompatiblity complex, expression of which is often lost by tumor cells. We assessed the ability of several antigen-binding domains in the context of CAR to bind αVb6, an integrin that is highly expressed on pancreatic cancer cells. A CAR incorporating a peptide from foot-and-mouth disease virus VP1 capsid protein, a human IgG Fc spacer region, a transmembrane spanning domain and a fusion of intracellular signaling domains from CD28 and CD3z provided the highest level of binding to αVb6. Primary T-cells were then engineered for CAR expression using the Sleeping Beauty transposon system. S63
CANCER-IMMUNOTHERAPY I Artificial antigen presenting cells expressing αVb6 integrin protein were engineered for specific expansion of CAR-expressing primary T cells. Functional activation of the assembled CAR in primary T-cells was determined by secretion of IFNg upon exposure of the engineered T cells to either αVb6 protein or αVb6+ pancreatic cancer cells. These results demonstrate the feasibility of assembling CAR to target αVb6 integrin and support anticipated antitumor activity of these cells in preclinical studies and ultimately in the treatment of human pancreatic cancer.
169. Clinically Adaptable CD19-Specific Chimeric Antigen Receptor
Iulia Diaconu,1 Barbara Savoldo,1 Gianpietro Dotti.1 1 Center for Cell and Gene Therapy, Baylor College of Medicine, Houston. Immunotherapy with CAR-redirected T-cells can cure CD19+ leukemias. However, the occurrence of cytokine storms, prolonged B-cell aplasia (> 18 months) and occurrence of Graft-versus-HostDisease (GvHD) when donor CAR-T cells are used after allogeneic hematopoietic stem cell transplant (HSCT) remain drawbacks. To address these limitations, we developed a new vector encoding 3 components: (1) CAR.CD19 including the 4-1BB endodomain; (2) the iCaspase9 (iC9) suicide gene, to eliminate transgenic cells in case of acute toxicity or GvHD, or to specifically terminate prolonged B-cell aplasia “on demand”; (3) the DNGFR marker, to select transgenic T-cells, when infused after allogeneic HSCT. In this study we compared the new iC9-DNGFR-CAR.CD19 (CAR-iC) vector with a vector encoding the same CAR.CD19 (CAR) alone. Transduction efficiency with the new vector was 63%±9% and, after the selection for NGFR, 98%±1% of the cells co-express CAR and DNGFR. Selected T-cells were expanded for 10 days in the presence of IL-7 and IL-15, and then tested for functionality. Both CAR-iC+ and CAR+ T-cells expanded well (median 230-fold and 320-fold, respectively). Cytotoxic activity based on 51Cr release assay, was comparable, with killing of CD19+ tumor targets (Raji) at an E:T ratio of 20:1 of 89%±13% with CAR-iC+ T cells versus 94%±9% with CAR+ T cells. Longer-term antitumor activity, assessed by coculture assays with Raji for 5 days, showed complete elimination of CD19+ tumor cells by both CAR-iC+ and CAR+ T cells at all ratios used. Functionality of the iC9 gene was assessed by exposing CARiC+ T-cells to CID which induced >98% apoptosis after 24 hrs, while control CAR+ T-cells remained unaffected. Finally, we performed experiments in vivo in NSG mice reconstituted with human-cord blood derived CD34+ cells. Upon engraftment of human B cells, HLA mismatched FireFly-Luciferase-labelled CAR-iC+ T-cells (5x106) were infused i.v. and their persistence monitored by IVIS imaging. CAR-iC+ T cells completely eliminated B cells in association with a concomitant expansion of T cells. As B-cell aplasia occurred, CARiC+ T cells subsequently contracted, even if bioluminescent signals remained detectable for >3 months, and T-cells were detectable in peripheral blood, spleen and bone marrow by flow cytometry. At the peak of T-cell expansion, with corresponding B-cell aplasia, a group of mice received one single dose of CID (50μg/mouse). This resulted in a rapid (<48hrs) and significant reduction and disappearance of the bioluminescent signal indicating elimination of circulating T cells, that was confirmed by FACS analysis. Reconstitution of B lymphocytes followed within 2 months. Our data support the advantages of our proposed CAR-iC vector for adoptive T-cell therapy of B-cell malignancies, offering efficient removal of T-cells in both the autologous and allogeneic settings with control of toxicities and termination “on demand” of prolonged and unwanted B-cell aplasia without loss of the antitumor response.
S64
170. Low MHC Class I Expression in Pediatric Malignancies May Impede Success of MHCDependent Immunotherapies
Kellie Haworth,1,2 Michael Arnold,1 Jennifer Leddon,2,3 Chun-Yu Chen,2 Timothy Cripe.1,2 1 Pediatric Hematology/ Oncology/ BMT, Nationwide Children’s Hospital, Columbus, OH; 2Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children’s Hospital, Columbus, OH; 3University of Cincinnati Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinatti, OH. Immunotherapies are gaining considerable traction with increasing reports of antitumor efficacy in some FDA-approved agents. Some strategies are MHC-independent, such as T-cells engineered to express chimeric receptors (CARs) and bi-specific antibodies (BiTEs), but others, such as cancer vaccines, are dependent upon recognition of antigenic peptides presented by major histocompatibility complexes (MHC). There is growing recognition that oncolytic viruses also exert their therapeutic effects in part by inducing an adaptive T-cell response against tumor-associated antigens. Although, the dependence on MHC Class I for the T-cell-dependent effects of oncolytic virotherapy is intuitive, and has not been formally addressed. Unfortunately, tumor cell interaction with the immune system is limited with the loss of tumor antigens, lack of chemokines, lack of adhesion molecules, lack of tumor vascularization, and loss of MHC Class I expression. For those types of immunotherapies which are dependent upon MHC Class I antigen presentation, it is important to know the MHC Class I expression on tumor cells, and, in the case of virotherapy, the effects of infection on MHC Class I expression. In adult cancers, MHC Class I expression has been extensively studied, with down-regulation seen in 40-90% of cases and associated with a poor prognosis. However, few studies have examined MHC Class I expression in pediatric cancers. As oncolytic virotherapy trials have expanded to the pediatric population, we sought to address this paucity of information and determine whether MHC Class I down-regulation may serve as a barrier to virotherapy and other MHC-restricted therapies. We queried mRNA expression microarray databases including clinical and preclinical datasets for MHC Class I expression. Our preliminary data suggest that sarcomas, including Ewing sarcoma, osteosarcoma, and both embryonal and alveolar rhabdomyosarcomas, Wilms’ tumors, and some brain tumors, such as AT/RT (atypical teratoid/ rhabdoid tumors) and ependymomas, also exhibit decreased MHC Class I mRNA levels relative to other cancer types. In some human rhabdomyosarcoma cell lines, we found that MHC Class I can be up-regulated in vitro, indicating a reversible epigenetic mechanism for down-regulation. Preliminary results in immunocompetent murine rhabdomyosarcoma models suggest that the in vivo therapeutic effect of oHSV is largely T-cell dependent and that the best therapeutic response, including complete tumor rejection and resistance to tumor re-challenge, correlated with the highest MHC Class I expression. We therefore believe that the establishment of MHC Class I assays will likely serve as important biomarkers for patient inclusion in therapeutic trials of MHC-dependent immunotherapies, and modulation of MHC Class I expression may be a promising strategy to enhance oncolytic virotherapy.
Molecular Therapy Volume 22, Supplement 1, May 2014 Copyright © The American Society of Gene & Cell Therapy