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Organ acceptance and rejection
“Of particular interest” in the opinion of immunologists. Papers “of particular interest” selected, from the previous year’s literature, by the authors of reviews in the sections on Transplantation and Cancer in the October 1992 issue of Current Opinion in immunology.
Organ accepta.nce Mark D. Pescovitz SMITH CV, ROSENGARD
and rejection
NAKAJIMA K, BR, FISH~EIN
selected
by
MIXON A, GUZZE’ITA PC, JM, SACHS DH: Success-
ful Induction of Long-Term Specific Tolerance to FuIIy AUogeneic Renal AIIografts in Miniature Swine. Transplantation 1992, 53~438-444. This paper demonstrates the potential of the mixed allogeneic chimera bone marrow transplant model in a large animal. The model is difficult to establish. So far it has only been successful in a partial MHC mismatch combination. It also iadicates that induction of tolerance to class II MHC may be the most critical phase. PRIESTLEYCA, SPENCER SC, SAWYER GJ, FABRE JW: Suppression of Kidney AIIograft Rejection Across FUR MHC Barriers by Recipient-Specific Antibodies to Class II MHC Antigens. Transplantation 1992, 53:10241032. These authors, by using principals from the new body of literature detailing the pathways of presentation of al loantigen, reexamined the model of antibody-mediated enhancement. They treated recipients with an antibody directed against the recipient class II MHC antigens. By blocking the indirect pathway of antigen presentation of alloantigens by recipient antigen-presenting cells, they achieved a marked prolongation of graft survival. Monoclonal antibodies in the detection and therapy of micIrometastatic epithelial cancers selected by Ge#rt Riethmiiller and Judith P. Johnson COTE RJ, ROSEN PP, LESSER ML, OLD LJ, OSBORNE MP: Prediction of Early Relapse in Patients with Operable Breast Cancer by Detection of Occult Bone Marrow Micrometastases. J Clin Oncol 1991, 9~17491756. The first study, employing cytokeratin antibodies, that demonstrates the predictive value of micrometastatic cells in bone marrow ‘of breast carcinoma patients. The total number of cells per aspirate appears to be important for the prognosis. GRAM H, MAFXOI\JIL-A, BARB& CF, COLLET TA, LERNER RA, KANG AS: In Vitro Selection and Affinity Maturation of Antibodies from a Naive Combinatorial ItnrnunogIobuIin Library. Proc NatE Acad Sci USA 1992, 89:35763580. An elegant demonstration of the isolation and ‘alfinity maturation’ of Fab fragments recognizing progesterone obtained from combinatorial libraries created from naive B lymphocytes. Combinatorial cDNA libraries were produced from l.i and x V region mRNA isolated
656
from the bone marrow cells of non-immune mice. From among the Fab fragments produced, some that bound to the antigen progesterone were selected. These antibodies had low affinity for the antigen; thus, the clones t;-ere subjected to random mutagenesis, which led to the ISOlation of clones with high affinity. These studies suggest that using this approach, high affinity antibodies to virtually any antigen can be isolated from non-immunized donors. B~CHLER M, FFZESS H, SCHULTHEISS KH, GEBHARDT C, K~~BEL R, MIJHRER KH, WINKELMANN M, WAGENEP ‘I’, KLA~DOR R, KAUL M, ET AL.: A Randomized Contro&.:d
Trial of Adjuvant Immunotherapy (Murine Monoclonal Antibody 494/32) in Resectable Pancreatic Cancer. Cancer 1991, 68:1507-1512. This is the first report of a prospective randomized multicenter trial with passive antibody therapy in a solid tumor in an ‘adjuvant’ situation (i.e. any therapy given after curative surgery) that shows no effect of the antibody on survival or interval between relapses. The minimal residual disease state of the majority of patients is questionable as the partial removal of the pancreas and duodenum may not have been complete in many patients. Monoclonal antibodies in the study and therapy of hematopoietic cancers selected by Dana C. Matthews, Franklin 0. Smith and Irwin D. Bernstein SL, KUNG AHC: EffiFISHWILDDM, ABERLE S, BERNHARD cacy of an Anti-CD7Ricin A Chain Immunoconjugate in a Novel Murine Model of Human T-Cell Leukemia. Cancer Res 1992, 52130563062. The efficacy of Anti-CD7-Ricin A chain conjugates in a mouse model of a human T-cell leukemia line (CEM) in NM-III mice is described, A lo&-200-fold depletion of leukemic cells from the spleen and marrow was achieved, compared with threefold depletion with anti-CD7 antibody alone. UCKUN FINNEGAN GUNTHER
FM,
MANIVEL C, TUELAHLGREN
ARTHUR D, L, IRVIN
CHELSTROM JD, MYERS
LM,
DE, In Vito Efficacy of B& (AntiCD 19~Fokeweed Antiviral Protein Immunotoxin Against Human Pre-B CeII Acute Lymphoblastic Leukemia in Mice with Severe Combined Immunodeficiency. Blood 1992, 79:2201-2214. In this impressive study, SCID mice were inoculated intravenously with a human pre-B-cell acute lymphoid leukemia line NALM-6 and treated with B43 (antiCDlg) conjugated with pokeweed antiviral protein immunotoxin. Treatment resulted in 6&65% survival. D, R:
@ 1992 Current
Biology
Organ accepta.nce Mark D. Pescovitz SMITH CV, ROSENGARD
and rejection
NAKAJIMA K, BR, FISH~EIN
selected
by
MIXON A, GUZZE’ITA PC, JM, SACHS DH: Success-
ful Induction of Long-Term Specific Tolerance to FuIIy AUogeneic Renal AIIografts in Miniature Swine. Transplantation 1992, 53~438-444. This paper demonstrates the potential of the mixed allogeneic chimera bone marrow transplant model in a large animal. The model is difficult to establish. So far it has only been successful in a partial MHC mismatch combination. It also iadicates that induction of tolerance to class II MHC may be the most critical phase. PRIESTLEYCA, SPENCER SC, SAWYER GJ, FABRE JW: Suppression of Kidney AIIograft Rejection Across FUR MHC Barriers by Recipient-Specific Antibodies to Class II MHC Antigens. Transplantation 1992, 53:10241032. These authors, by using principals from the new body of literature detailing the pathways of presentation of al loantigen, reexamined the model of antibody-mediated enhancement. They treated recipients with an antibody directed against the recipient class II MHC antigens. By blocking the indirect pathway of antigen presentation of alloantigens by recipient antigen-presenting cells, they achieved a marked prolongation of graft survival. Monoclonal antibodies in the detection and therapy of micIrometastatic epithelial cancers selected by Ge#rt Riethmiiller and Judith P. Johnson COTE RJ, ROSEN PP, LESSER ML, OLD LJ, OSBORNE MP: Prediction of Early Relapse in Patients with Operable Breast Cancer by Detection of Occult Bone Marrow Micrometastases. J Clin Oncol 1991, 9~17491756. The first study, employing cytokeratin antibodies, that demonstrates the predictive value of micrometastatic cells in bone marrow ‘of breast carcinoma patients. The total number of cells per aspirate appears to be important for the prognosis. GRAM H, MAFXOI\JIL-A, BARB& CF, COLLET TA, LERNER RA, KANG AS: In Vitro Selection and Affinity Maturation of Antibodies from a Naive Combinatorial ItnrnunogIobuIin Library. Proc NatE Acad Sci USA 1992, 89:35763580. An elegant demonstration of the isolation and ‘alfinity maturation’ of Fab fragments recognizing progesterone obtained from combinatorial libraries created from naive B lymphocytes. Combinatorial cDNA libraries were produced from l.i and x V region mRNA isolated
656
from the bone marrow cells of non-immune mice. From among the Fab fragments produced, some that bound to the antigen progesterone were selected. These antibodies had low affinity for the antigen; thus, the clones t;-ere subjected to random mutagenesis, which led to the ISOlation of clones with high affinity. These studies suggest that using this approach, high affinity antibodies to virtually any antigen can be isolated from non-immunized donors. B~CHLER M, FFZESS H, SCHULTHEISS KH, GEBHARDT C, K~~BEL R, MIJHRER KH, WINKELMANN M, WAGENEP ‘I’, KLA~DOR R, KAUL M, ET AL.: A Randomized Contro&.:d
Trial of Adjuvant Immunotherapy (Murine Monoclonal Antibody 494/32) in Resectable Pancreatic Cancer. Cancer 1991, 68:1507-1512. This is the first report of a prospective randomized multicenter trial with passive antibody therapy in a solid tumor in an ‘adjuvant’ situation (i.e. any therapy given after curative surgery) that shows no effect of the antibody on survival or interval between relapses. The minimal residual disease state of the majority of patients is questionable as the partial removal of the pancreas and duodenum may not have been complete in many patients. Monoclonal antibodies in the study and therapy of hematopoietic cancers selected by Dana C. Matthews, Franklin 0. Smith and Irwin D. Bernstein SL, KUNG AHC: EffiFISHWILDDM, ABERLE S, BERNHARD cacy of an Anti-CD7Ricin A Chain Immunoconjugate in a Novel Murine Model of Human T-Cell Leukemia. Cancer Res 1992, 52130563062. The efficacy of Anti-CD7-Ricin A chain conjugates in a mouse model of a human T-cell leukemia line (CEM) in NM-III mice is described, A lo&-200-fold depletion of leukemic cells from the spleen and marrow was achieved, compared with threefold depletion with anti-CD7 antibody alone. UCKUN FINNEGAN GUNTHER
FM,
MANIVEL C, TUELAHLGREN
ARTHUR D, L, IRVIN
CHELSTROM JD, MYERS
LM,
DE, In Vito Efficacy of B& (AntiCD 19~Fokeweed Antiviral Protein Immunotoxin Against Human Pre-B CeII Acute Lymphoblastic Leukemia in Mice with Severe Combined Immunodeficiency. Blood 1992, 79:2201-2214. In this impressive study, SCID mice were inoculated intravenously with a human pre-B-cell acute lymphoid leukemia line NALM-6 and treated with B43 (antiCDlg) conjugated with pokeweed antiviral protein immunotoxin. Treatment resulted in 6&65% survival. D, R:
@ 1992 Current
Biology