Non-Cytotoxic Therapeutics: Past and Future

Abstract:

Advances continue to be made in tumor immunology and in strategies to integrate the growing number of bioimmunotherapeutic molecules into the treatment of ovarian cancer as well as other malignancies. Extensive studies have provided support for antigendriven T-cell activation in vivo. The number of known tumor antigen epitopes is expanding although advances in this area remain behind that of melanoma. Evidence also suggests that the tumor environment is contributing to a state of in vivo immunosuppression; however, in vitro experiments and laboratory correlative studies also suggest that immune suppressor activity might be reversible. These findings could lead to new approaches, such as the use of antibodies or cytokines to overcome the immunosuppressive effects, in addition to the more established surgical and chemotherapeutic debulking.

Both prophylactic and therapeutic bioimmunotherapeutic strategies require pharmacodynamic and immunologic end points that can guide each phase in the development of an effective approach. Review of systemic and intraperitoneal immunotherapy trials of interferon alpha, gamma and IL2 as well as newer agents, such as IL12 and Flt3-Ligand, overall continues to offer promise of a role for bioimmunotherapy in the treatment of ovarian cancer. Future developments lie in improved target specificity of activated cells and cell surface binding molecules and a systematic plan for combining chemotherapy with cytokines, growth factors and polyvalent vaccines that are based on the in vivo dynamics of each agent. Another totally different approach, which could set a new paradigm, might be to target cells from the inflammatory immune system which could contribute to tumor growth, invasion, and metastasis.