A Look Toward The Future

by Harry Zhabilov

Even as we test these early vaccine approaches in patients, new and more potent vaccine approaches and being developed in preclinical models. These approaches employ tumor-associated antigens either in the form of proteins or peptides mixed with defined adjuvants administered intradermally or subcutaneously or as genes expressed in viral vectors administered systemically. Antigen-based vaccines get rid of the need for the genetic manipulation of tumor cells. This simplifies the vaccine production process and should result in more generalizable vaccines allow for greater control over the amount of antigen formulated in the vaccine, which should translate into improved efficacy. In fact, some of these strategies have been demonstrated in preclinical models to be magnitudes more potenet than a whole cell of vaccine approach. Recent advances in molecular biology have allowed the direct isolation of tumor-associated antigens that are the targets of cytotoxic T cells. Tumorassociated antigens have now been identified for several cancers including adenocarcinoma of the breast, colon, and pancreas, as well as for malignant melanoma. These antigens can be classified by tissue distribution and function (Table 1). Many of these antigens have been found to be shared among other patients’ tumors of the same histologic site. These shared antigens are potential candidates for vaccine development. Several of these antigens are binding in vitro or mixed with defined IPFs or pulsed directly onto autologous dendritic cells (Professional APCs) that are activated in vivo in each patient’s. Future immunotherapy of cancer approaches will probably employ newly identified tumor-associated antigens bind with IPF-s that are delivered in patients with different type of cancer. The conduction of well controlled clinical trials will be necessary to identify the most effective approaches for the treatment of advanced cancer. More than likely, it will be necessary to combine vaccine approaches with other cancer treatment as IL-10 cytokines, Th1 MHC class II antigens, and co-stimulatory molecules macrophages .modalities to effectively treat larger metastases.

Antigen Category Human Tumor Antigens
Mutated gen products for melanoma Cyclin-dependent kinase
Cell carcinoma of head and neck Mutated intron B33-B
Reactivated silent gene B-catenin
Melanoma MAGE gene family
Melanoma BAGE gene family
Tissue-specific antigens (different antigens) Tyrosinase (melanoma) Melan-A/MART-1
Melanoma Gp100 (melanoma)
Idio-typic epitopes Gp75 (melanoma)
Viral gene products Ig (B cell lymphoma)
Oncogene products (CML) TCR (T lymphoma)
Products ( pancreas and colorectal cancer EBV ( Burkitt’s Lymphoma)
Overexpression (brest,lung,ovarian cancers) HPV (cervical cancer)
Mutated tumor suppressor HBV (hepatoma)
Products (most cancer) HER-2/neu
Gene products Mutated p53 gene

Table 1. Categories of identified human tumor antigens