Autologous tumor antigens

Adoptive dendritic cell-based immunotherapy represents a promising approach to overcoming peripheral tolerance against autologous tumor antigens and to maintaining protective antitumor immunity. The translation of successful preclinical studies, however, appears to be hampered by new complexities associated with the clinical situation. 

The active immunotherapeutic approach is specific and based on the premise that tumor antigens are immunogenic and the host is sufficientiy immunocompetent to mount an effective immune response to an autologous tumor. Theoretically, a weak or suppressed host immune system that had allowed the formation of a tumor may be overridden by active immunization or immunostimulation. In practice, vaccines composed of so-called autologous tumor extracts have been used to treat patients with malignant melanoma (73), and purified melanoma tumor-associated antigens have been used to ehcit antibody responses in melanoma patients (74). 

Tumor Vaccines. Autologous or allogenic tumor cells which are administered as vaccine (e.g., tumor cell lines tumor cell lysates primary explant). This group also includes autologous antigen presenting cells pulsed with tumor specific peptides or tumor cell lysates. 

Figure 6 Immunopotentiating reconstituted influenza virosomes (IRIV) adjuvant effects in the induction of tumor associated antigen-specific cytotoxic T cell. CD14-negative cells from a healthy donor peripheral blood mononuclear cells were cocultured with autologous immature dendritic cells (iDC) in the presence of Melan-A/Mart-l27-35, alone (A) or supplemented with either control liposomes (B) or IRIV (1 50, C). On day 7, culture cells were restimulated with Melan-A/MART-127-35 pulsed iDC and cultured for six further days [see Materials and Methods ]. On day 7 after restimulation cells were stained with fluorescein isothiocyanate-conjugated anti-CD8 and phosphatidylethanolamine-conjugated HL A-A0201 /Melan-A/MART -127-3 5 tetramers. Source From Ref. 6.

In cancer, host antibodies react with a unique group of autologous intracellular proteins known as tumor-associated antigens (TAAs). Additionally, autoimmunity is consistently observed in a variety of well-known autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and insulin-dependent diabetes mellitus. The detection of autoimmunity is useful because autoantibodies can serve as biomarkers for disease, and their presence may help to elucidate the role of significant disease-related biochemical pathways. 

Both of MAGE and GAGE gene families encode different tumor-associated antigenic peptides recognized by the autologous cytotoxic T-lymphocytes. 

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