Immunotherapy of cancer

Immunotherapy of cancer

The aim of immunotherapy is to induce or potentiate inherent anti­ tumor immunity that can destroy cancer cells. Central to the process of antitumor immunity is the ability of the immune system to rec­ognize tumor-associated antigens present on human cancers and to direct cytotoxic responses through humoral or T-cell-mediated immunity. Overall, T-cell-mediated immunity appears to have the greater potential of the two for eradicating tumor cells. T cells rec­ognize antigens on the surfaces of target cells as small peptides presented by class I and class 11major histocompatibility complex (MHC) molecules
.

Antitumor strategies that have been investigated . One approach to antitumor immunity is non specific immunotherapy, which stimulates the immune system as a whole by administering bacterial agents or their products, such as bacille Calmerte-Guerin (BCG). This approach is thought to activate the effectors of antitumor response such as natural killer cells and macrophages, as well as polyclonal lymphocytes. Another ap­proach to non specific immunotherapy is systemic administration of cytokines such as IL-2, interferon alpha, and interferon gamma. IL-2 stimulates proliferation of cytotoxic T lymphocytes and maturation of effectors such as natural killer cells into lymphokine-activated

killer cells. interferons, on the hand. exert antitumor effects directly­
(by inhibiting tumor cell proliferation), indirectly (by acti­vating host immune cells including macrophages, dendritic cells, and natural killer cells), and by enhancing human leukocyte antigen (HLA) class I expression on tumor cells.

Antigen-specific immunotherapy can be active, achieved through antitumor vaccines, or passive. In passive immunotherapy, antibodies to specific tumor-associated antigens can be produced by hybridoma technique and then administered to patients whose cancers express these antigens, inducing antibody-dependent cellular cytotoxicity.

The early attempts at vaccination against cancers utilized allo­ -geneic cultured cancer cells, including irradiated cells, cell lysates, or shed antigens isolated from tissue culture supernatants. An alternate strategy is the use of autologous tumor vaccines, which have the potential advantage of being more likely to contain antigens relevant for the individual patient, but have the disadvantage of needing­
a large amount of tumor tissue for preparation, which restricts ­ eligibility of patients for this modality. Strategies to enhance immuno­genicity of tumor cells include the introduction of genes encoding cytokines chemokinase or fusion of the tumor cells to allogeneic MHC11- bearing cells alternatively heat shock proteins derived from a patient,s tumour can be utilized as heat shock protein peptide complexes are readily taken up by dendritic cells for presentation to T cells identification of tumour antigens has made it possible to perform antigen specific vaccination tumour antigen recognized by T cells fall into several categories
vaccines directed at defined tumour antigens aim to combine selected tumour antigen and appropriate routes for delivering these antigens to the immune system to optimize antitumor immunity in adoptive transfer antigen specific ie cytotoxic T lymphocytes or antigen non specific ie natural killer cells effector cells

can be transferred to a patient.these effector cells can be obtained from the tumor (tumor-infiltrating lymphocytes) or the peripheral blood.

Clinical experience in patients with metastatic disease has

shown objective tumor responses to a variety of immunotherapeutic modalities. is thought, however, that the immune system is over­ whelmed with the tumor burden in this setting. and thus adjuvant therapy may be preferable. reserving immunotherapy for decreasing tumor recurrences. Trials to date suggest that immunotherapy is a potentially useful approach in the adjuvant setting. How to best select patients for this approach and how to integrate immunother­apy with other therapies are not well understood for most cancer types.

Categories and Examples of Tumour associated Antigens Recognized by Human T cells
 

Cancers expression the antigens	Tumour antigens	Category
MELANOMA breast head and neck bladder gastric and lung cancers	MAGE-1 MAGE-2,3,12 BAGE ,GAGENY-ESO-1	Cancer testis
melanoma	Tyrosinase TRP-1,TRP-2,MART-1,MCIR	Differntiation antigens
CML CML ALL AML COLON breat lung pancreas cancers Breast ovary lung cancers Liver cancer	Proteinase3 WT1 CEA Her2|neu Alpha-fetoprotein	Overexpressed self antigens
B-cell,NHL,MM Melanoma Head and neck cancer Colorectal lung bladder head and neck cancers	Immunoglobin idiotype Caspase-8 Beta-catenin Mutated p53	Tumour specific antigens
CERVICAL AND PENILE CANCERS EBV+,Hodgkins disease Liver cancer Kaposi,s sarcoma	HPVE6|E7 EBV LMP2a HCV HHV-8	Viral antigens

tags:immunotherapy,cancer