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Updated: Jun 6, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Clinical studies with anti-CTLA-4 antibodies in non-melanoma indications
Luana Calabrò1, Riccardo Danielli, Luca Sigalotti
1Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. l.calabro@ao-siena.toscana.it
Abstract:
Available medical treatments have limited impact on the survival of patients with advanced cancer; therefore, new therapeutic strategies able to generate more effective host's immune responses against neoplastic cells are being actively pursued. Among these, a recent approach involves targeting of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a key immune checkpoint molecule, by monoclonal antibodies (mAbs). Ipilimumab and tremelimumab represent the prototypes of this new class of immunomodulating mAb and have been extensively tested in metastatic melanoma with highly promising results. The clinical activity observed in melanoma has served as a model to exploit the therapeutic potential of CTLA-4 blockade in a variety of human malignancies. Along this line, early-phase trials with anti-CTLA-4 mAbs have been completed or are ongoing in tumors of different histotype. Results are demonstrating the feasibility, safety, and activity of these agents, thus suggesting a promising therapeutic role to be further investigated in phase II/III trials in a wide range of tumors. This review summarizes the main trials with ipilimumab and tremelimumab in tumors of different histotypes, excluding cutaneous melanoma, which is extensively described in other chapters of this issue of Seminars in Oncology.
Insights
New immunotherapies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) show promise for advanced cancers. Monoclonal antibodies like ipilimumab and tremelimumab are being investigated for their potential to enhance immune responses against tumors beyond melanoma.
Area of Science:
- Oncology
- Immunology
Background:
- Advanced cancer treatments have limited efficacy.
- Novel strategies enhancing host anti-tumor immune responses are crucial.
- Immune checkpoint inhibitors, particularly targeting CTLA-4, represent a promising therapeutic avenue.
Purpose of the Study:
- To review clinical trials of anti-CTLA-4 monoclonal antibodies (mAbs) in various human malignancies.
- To summarize the safety, feasibility, and activity of ipilimumab and tremelimumab in non-melanoma tumors.
- To assess the therapeutic potential of CTLA-4 blockade in a broad spectrum of cancers.
Main Methods:
- Review of early-phase clinical trials involving ipilimumab and tremelimumab.
- Analysis of data from ongoing and completed trials in diverse tumor types.
- Exclusion of data pertaining to cutaneous melanoma to focus on other histotypes.
Main Results:
- Anti-CTLA-4 mAbs demonstrate feasibility and safety in early-phase trials.
- These agents exhibit promising activity in various human malignancies.
- Clinical activity observed in melanoma serves as a model for other cancers.
Conclusions:
- CTLA-4 blockade with ipilimumab and tremelimumab holds significant therapeutic potential for advanced cancers.
- Further investigation in phase II/III trials is warranted across a wide range of tumors.
- These immunomodulating mAbs offer a new strategy to improve patient survival in various malignancies.
