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Biologic and immunologic therapies for ovarian cancer
Jonathan S Berek1, Birgit C Schultes, Christopher F Nicodemus
1Division of Gynecologic Oncology, David Geffen School of Medicine at University of California Los Angeles, UCLA Center for the Health Sciences, Los Angeles, CA 90095-1740, USA. jberek@mednet.ucla.edu
Abstract:
Biologic therapy of ovarian cancer has been conducted using nonspecific biologic response modifiers, cytokines, monoclonal antibodies (MAbs), vaccines, and gene therapy. Antibodies directed toward her2/neu have also been studied. Phase I and II gene therapy trials using adenoviral vectors containing a wild-type or modified p53 have shown that the treatment is well tolerated. Phase II and III trials are ongoing with MAbs directed against CA-125 (MAb B43.13) and an antibody directed against HMFG1 (anti-HMFG1-yttrium-90-labeled antibody). The trials have shown that these agents are well tolerated and that immunologic responses occur, although the ultimate clinical value of these agents remains to be determined. Prolonged survival after MAb B43.13 treatment has been correlated with changes in several immune parameters, including human antimurine antibody, Ab2, anti-CA-125 antibody development, and induced T-cell immunity. Clinical trials using a MAb directed toward the encoded products of her2/neu have shown minimal activity against ovarian cancer in a phase I and II trial conducted by the Gynecologic Oncology Group. Cytokine therapies have been administered systemically and intraperitoneally. Intracavitary interferon alfa, interferon gamma, and interleukin-2 alone or in combination with cytotoxic therapy in phase I and II trials demonstrated intraperitoneal lymphoid cell stimulation and produced antitumor responses. A randomized trial of chemotherapy with or without interferon gamma in primary treatment produced a response and a progression-free survival advantage in the arm that incorporated the interferon gamma, without a statistically significant benefit in overall survival. A phase III study of interferon gamma in combination with first-line chemotherapy is currently ongoing.
Insights
Biologic therapies, including monoclonal antibodies and cytokines, show promise in ovarian cancer treatment by stimulating immune responses. While well-tolerated, their ultimate clinical value and impact on survival require further investigation.
Area of Science:
- Oncology
- Immunotherapy
- Biologic Therapy
Background:
- Ovarian cancer treatment has explored various biologic therapies, including nonspecific biologic response modifiers, cytokines, monoclonal antibodies (MAbs), vaccines, and gene therapy.
- Antibodies targeting her2/neu and CA-125 have been investigated, alongside p53 gene therapy and cytokine-based treatments.
Purpose of the Study:
- To review the current landscape and clinical trial outcomes of biologic therapies for ovarian cancer.
- To assess the tolerability, immunogenicity, and preliminary efficacy of different biologic agents.
Main Methods:
- Review of Phase I, II, and III clinical trials involving gene therapy (p53), monoclonal antibodies (anti-CA-125, anti-HMFG1, anti-her2/neu), and cytokines (interferon alfa, interferon gamma, interleukin-2).
- Analysis of treatment tolerability, immune parameter changes, and clinical outcomes such as response rates, progression-free survival, and overall survival.
Main Results:
- Gene therapy with p53 was well-tolerated in Phase I/II trials.
- Monoclonal antibody trials (MAb B43.13) showed tolerability, induced immune responses, and correlated prolonged survival with immune parameter changes.
- Cytokine therapies demonstrated intraperitoneal lymphoid cell stimulation and antitumor responses; interferon gamma showed a response and progression-free survival advantage in a randomized trial.
Conclusions:
- Biologic therapies, including MAbs and cytokines, are generally well-tolerated and can elicit immune responses in ovarian cancer patients.
- While some agents like MAb B43.13 and interferon gamma show potential benefits, their definitive clinical value and impact on overall survival are still under investigation.
- Further research and ongoing Phase III trials are crucial to establish the role of these immunotherapeutic agents in ovarian cancer treatment.