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Molecular vaccines in infection and cancer
Leukmro Rereorch Vol. 20, No. 4, pp. 365-366, 1996. Copyright 0 1996 Elsevier Science Ltd. All rights reserved Printed in Great Britain 014552126/96 $15.00 + 0.00
Pergamon 01452126(95)00088-7
MEETING MOLECULAR
VACCINES
REPORT
IN INFECTION
AND CANCER
reactive immunity which will act against a range of influenza viruses has obvious attractions. The EpsteinBarr virus is a clear candidate for vaccine development, with relevance for cancer, and Andrew Morgan (Bristol, U.K.) discussed results of using the envelope gp340 as an immunogen in a monkey model. The expression system used to produce the gp340 protein was critical, and it will be interesting to consider whether the DNA vaccine approach would be applicable to this vaccine also. Malaria is a major scourge, and Adrian Hill (Oxford, U.S.A.) reviewed his fascinating findings indicating that certain MHC Class I antigens may have been conserved to present protective peptides to the immune system. Here, rational design of peptides looks promising and options for presenting chosen peptides as vaccines were discussed; again, one of these was to use a DNA vaccine. Vaccination against cancer must lag behind infectious diseases, but encouraging preliminary results are already available for carcinoembryonic antigen (CEA) which is expressed by several tumours. Using mouse models, David Curie1 (Alabama, U.S.A.) described induction of protective immunity against colonic carcinoma by vaccination with DNA encoding CEA. Interestingly, immunity could be promoted by adding in cytokineencoding plasmids. For B-cell tumours, idiotypic protein vaccination is known to generate protective immunity, but the difficulty for patients has been in the requirement for ‘personal’ vaccines. The use of DNA plasmids encoding idiotypic protein has simplified the approach to the point of a small clinical trial. Addition of cytokineencoding vectors again provides a means of stimulating appropriate immune pathways to generate effective antitumour immunity, which may be necessary in patients with disease. Finally, melanoma provides a cancer with candidate antigens for generation of immunity. Stimulation of natural immunity may require only delivery of a suitable cytokine, and Mary Collins (London, U.K.) described the protocol for transferring cytokine genes into tumour cells; the effects of this approach are being assessedin a clinical trial. Richard Vile (London, U.K.) wound up by sharing his experiences of inserting the B7 gene (bad
A Meeting on Molecular Vaccines in Infection and Cancer was held on May Day 1995 at the RSM. The bicentenary of Edward Jenner’s successful use of vaccination against smallpox is due in 1996, and it is particularly satisfying that it coincides with a leap in interest in vaccination. One of the reasons for this is that the exciting possibility for vaccinating against cancer is now on the agenda. The idea of the organizer of the meeting (Freda Stevenson, Southampton, U.K.) was to bring together speakers who are active in the field of infectious diseases, and who have a wealth of experience in designing effective vaccines, together with those who hope to apply the approach to cancer. The current crossfertilization of ideas and technology is focused particularly on the use of naked DNA vaccines. The miraculous ability of injected plasmid DNA to induce an immune response against the encoded protein could simplify vaccine formulations for infectious diseases. For cancer, DNA plasmids provide the opportunity to design and test efficacy of potential tumour antigens, and to direct these antigens into relevant pathways of antigen processing. The meeting opened with a review of vaccine design for use against bacterial meningitis, by John Heckels (Southampton, U.K.). The days of using crude vaccines are clearly numbered, and details illustrating the molecular nature of the relevant epitopes which will induce specific protective immunity were presented. Peter Beverley (London, U.K.) spoke about human papilloma virus, and was concerned with the mode of induction of a cytotoxic T cell response. It is clearly important to harness and promote this response which may arise via naturally processed peptides from infected keratinocytes. Rational design of candidate peptides for vaccines is attractive, but the pitfalls of this approach were ably illustrated by Hans Stauss (London, U.K.). The approach of using DNA vaccines against influenza has been pioneered by scientists at the Merck Company in Pennsylvania, U.S.A. and the amazing efficacy of the plasmid approach was demonstrated by John Donnelly. The possibility of generating cross365
366
Meeting Report
news) or the HSVtk gene (good news with gangciclovir) for generating an anti-melanoma attack in a mouse model. Clearly there are interesting times ahead in the development of vaccines against cancer, and we shall soon need the courage of Jenner (and James Phipps) to test clinical efficacy.
Freda Stevenson Molecular Immunology Group Tenorus Laboratory Southampton University Hospitals Tremona Road Southampton SO16 6YD U.K.
Pergamon 01452126(95)00088-7
MEETING MOLECULAR
VACCINES
REPORT
IN INFECTION
AND CANCER
reactive immunity which will act against a range of influenza viruses has obvious attractions. The EpsteinBarr virus is a clear candidate for vaccine development, with relevance for cancer, and Andrew Morgan (Bristol, U.K.) discussed results of using the envelope gp340 as an immunogen in a monkey model. The expression system used to produce the gp340 protein was critical, and it will be interesting to consider whether the DNA vaccine approach would be applicable to this vaccine also. Malaria is a major scourge, and Adrian Hill (Oxford, U.S.A.) reviewed his fascinating findings indicating that certain MHC Class I antigens may have been conserved to present protective peptides to the immune system. Here, rational design of peptides looks promising and options for presenting chosen peptides as vaccines were discussed; again, one of these was to use a DNA vaccine. Vaccination against cancer must lag behind infectious diseases, but encouraging preliminary results are already available for carcinoembryonic antigen (CEA) which is expressed by several tumours. Using mouse models, David Curie1 (Alabama, U.S.A.) described induction of protective immunity against colonic carcinoma by vaccination with DNA encoding CEA. Interestingly, immunity could be promoted by adding in cytokineencoding plasmids. For B-cell tumours, idiotypic protein vaccination is known to generate protective immunity, but the difficulty for patients has been in the requirement for ‘personal’ vaccines. The use of DNA plasmids encoding idiotypic protein has simplified the approach to the point of a small clinical trial. Addition of cytokineencoding vectors again provides a means of stimulating appropriate immune pathways to generate effective antitumour immunity, which may be necessary in patients with disease. Finally, melanoma provides a cancer with candidate antigens for generation of immunity. Stimulation of natural immunity may require only delivery of a suitable cytokine, and Mary Collins (London, U.K.) described the protocol for transferring cytokine genes into tumour cells; the effects of this approach are being assessedin a clinical trial. Richard Vile (London, U.K.) wound up by sharing his experiences of inserting the B7 gene (bad
A Meeting on Molecular Vaccines in Infection and Cancer was held on May Day 1995 at the RSM. The bicentenary of Edward Jenner’s successful use of vaccination against smallpox is due in 1996, and it is particularly satisfying that it coincides with a leap in interest in vaccination. One of the reasons for this is that the exciting possibility for vaccinating against cancer is now on the agenda. The idea of the organizer of the meeting (Freda Stevenson, Southampton, U.K.) was to bring together speakers who are active in the field of infectious diseases, and who have a wealth of experience in designing effective vaccines, together with those who hope to apply the approach to cancer. The current crossfertilization of ideas and technology is focused particularly on the use of naked DNA vaccines. The miraculous ability of injected plasmid DNA to induce an immune response against the encoded protein could simplify vaccine formulations for infectious diseases. For cancer, DNA plasmids provide the opportunity to design and test efficacy of potential tumour antigens, and to direct these antigens into relevant pathways of antigen processing. The meeting opened with a review of vaccine design for use against bacterial meningitis, by John Heckels (Southampton, U.K.). The days of using crude vaccines are clearly numbered, and details illustrating the molecular nature of the relevant epitopes which will induce specific protective immunity were presented. Peter Beverley (London, U.K.) spoke about human papilloma virus, and was concerned with the mode of induction of a cytotoxic T cell response. It is clearly important to harness and promote this response which may arise via naturally processed peptides from infected keratinocytes. Rational design of candidate peptides for vaccines is attractive, but the pitfalls of this approach were ably illustrated by Hans Stauss (London, U.K.). The approach of using DNA vaccines against influenza has been pioneered by scientists at the Merck Company in Pennsylvania, U.S.A. and the amazing efficacy of the plasmid approach was demonstrated by John Donnelly. The possibility of generating cross365
366
Meeting Report
news) or the HSVtk gene (good news with gangciclovir) for generating an anti-melanoma attack in a mouse model. Clearly there are interesting times ahead in the development of vaccines against cancer, and we shall soon need the courage of Jenner (and James Phipps) to test clinical efficacy.
Freda Stevenson Molecular Immunology Group Tenorus Laboratory Southampton University Hospitals Tremona Road Southampton SO16 6YD U.K.