Viral oncolysates in cancer treatment: immunological mechanisms of action (review).
Viral oncolysates (VO) are homogenates of virus-infected tumor cells. VO have been demonstrated in experimental animals to induce protection against transplanted autologous tumors, when administered prior to the challenge with the tumor. VO were first introduced into clinical trials as a treatment adjunct to chemotherapy and nonspecific immunomodulators (BCG). In recent years, beneficial clinical and biological activity responses have been observed in melanoma and gynecologic cancer (cervix, ovary), after administration of VO alone. Our group has continued clinical trials with PR8 strain influenza A. We have demonstrated that PR8 VO augments delayed type hypersensitivity in coded skin testing and have emphasized regional active immunization in treatment protocols. The efficacy of active immunization strategies have yet to be defined, but recent findings in ovarian and uterine cervix cancer highlight the importance of route and careful integration with other therapeutic modalities. The VO are postulated to trigger immunological mechanisms in the host that may ultimately lead to the control of the metastatic spread and elimination of the tumor. Humoral immune responses induced by VO have been described, while cellular immune responses associated with VO administration have been investigated to a lesser extent. We present here what is known and we discuss hypothesized mechanisms of humoral and T cell mediated immunity induced by VO now under investigation. The elucidation of these mechanisms may provide conceptual advances in the field of human tumor immunity as well as a rationale for the development of tumor vaccines.
Ioannides
C G
CG
Department of Gynecology, University of Texas M.D. Anderson Cancer Center 77030.
Platsoucas
C D
CD
O'Brian
C A
CA
Patenia
R
R
Bowen
J M
JM
Wharton
J T
JT
Freedman
R S
RS
D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D007109:Immunity; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014765:Viral Vaccines / Q000627:therapeutic use*
D014765:Viral Vaccines