Trends in Molecular Medicine
ReviewVaccines for colorectal cancer
Section snippets
Advances in tumor immunology
The two most significant advances in the field of tumor immunology in the past ten years are (1) the isolation and molecular characterization of the TAAs that are recognized by T cells, and (2) the elucidation of the molecular events that lead to T-cell-activation. Our expanded understanding of the molecular structure and function of these two systems has ledtomore refined and directed cancer vaccine development.
Whole tumor cell vaccine
Until all of the TAAs for a particular cancer can be quickly isolated and characterized, many investigators believe that the best source of antigen is the tumor itself. The main advantage of this approach is that all of the antigens (unique, as well as shared) expressed by a particular cancer are presented to the immune system. However, a potential disadvantage of this technique is that the most immunologically-relevant antigens might be underexpressed on the tumor cell and thus
Antigen-specific strategies
The precise molecular identification of TAAs has allowed for the development of more refined vaccination strategies. Successful immunization to specific TAAs in pre-clinical models has been demonstrated through a variety of mechanisms (Table 3), including: (1) recombinant viral vectors 32, 33; (2) peptide vaccines 34, 35; (3) antigen loaded dendritic cell vaccines 36, 37; (4) anti-idiotypic antibody vaccination 38;(5) DNA/RNA based vaccines 39; and (6) Immunization with heat shock proteins 40.
Anti-idiotypic antibodies to colorectal TAAs
Another approach for the development of both cellular and humoral immune responses to known TAAs is the use of anti-idiotypic antibodies. Based on the network hypothesis of Lindermann 54 and Jerne 55 any epitope could be converted into idiotypic determinants expressed on antibodies. Anti-idiotypic antibodies that share sequence homologies with nominal colorectal TAA could act as functional mimics of T-cell-antigens and stimulate cellular immune responses.
The best-characterized anti-idiotypic
Conclusions
Recent advances in the field of tumor immunology have expanded our understanding of the nature of tumor-associated antigens and mechanisms of T-cell activation. It is now clearly recognized that tumor cells express antigens that can be recognized by T cells. These antigens are derived from a variety of intracellular proteins. Successful activation of T-cell response to these antigens requires that they be presented in the context of the appropriate co-stimulatory signals. Current clinical
References (58)
From TCR engagement to T-cell activation: a kinetic view of T cell behavior
Cell
(1999)- et al.
T-cell costimulation via CD28–CD80/CD86 and CD40–CD40 ligand interactions
Res. Immunol.
(1995) An innate sense of danger
Semin. Immunol.
(1998)Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial
Lancet
(1999)A phase I trial of a synthetic mucin peptide vaccine. Induction of specific immune reactivity in patients with adenocarcinoma
J. Surg. Res.
(1996)Cancer statistics
Cancer J. Clin.
(2000)- et al.
Adjuvant therapy of colon cancer
Semin.Oncol.
(1999) - et al.
Third Keystone Symposium on cellular immunology and the immunotherapy of cancer
J. Immunother.
(1998) Development of cancer immunotherapies based on identification of the genes encoding cancer regression antigens
J.Natl Cancer Inst.
(1996)- et al.
Tumor recognition by the cellular immune system: new aspects of tumor immunology
Int. Rev. Immunol.
(1997)
Class I MHC molecules: assembly and antigen presentation
Immunol. Rev.
The role of B7 costimulation in T-cell immunity
Immunol. Cell Biol.
CD40–CD40 ligand
J. Leukoc. Biol.
CD27–CD70 interactions regulate T dependent B cell differentiation
Immunol. Res.
Dendritic cells in cancer immunotherapy
Annu. Rev. Immunol.
The critical role of CD40/CD40L in the CD4-dependent generation of CD8+ T cell immunity
J. Leukoc. Biol.
Adjuvant active specific immunotherapy for human colorectal cancer: 6.5-year median follow-up of a phase III prospectively randomized trial
J. Clin. Oncol.
Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283
J.Clin. Oncol.
Delayed cutaneous hypersensitivity to autologous tumor cells in colorectal cancer patients immunized with an autologous tumor cell: Bacillus Calmette–Guerin vaccine
Cancer Res.
Prospectively randomized trial of adjuvant active-specific immunotherapy for human colorectal cancer
Cancer
Meta analysis of threerandomized trials of active specific immunotherapy (ASI) of colon cancer
Proc. Am. Soc. Clin. Oncol.
Interaction of dendritic cells with mycobacteria: where the action starts
Immunol. Cell Biol.
Paracrine cytokine adjuvants in cancer immunotherapy
Annu. Rev. Immunol.
Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity
Proc. Natl. Acad. Sci. U. S. A.
Phase I study of non-replicating autologous tumor cell injections using cells prepared with or without GM–CSF gene transduction in patients with metastatic renal cell carcinoma
Hum. Gene Ther.
Novel allogeneic granulocyte–macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation
J. Clin. Oncol.
A phase I clinical trial of lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF gene for the treatment of pancreatic adenocarcinoma
Hum. Gene Ther.
Treatment of liver metastases from colon carcinoma with autologous tumor vaccine expressing granulocyte-macrophage colony-stimulating factor
J. Surg. Oncol.
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