Combination of Immune Checkpoint Therapy with Cancer Vaccine

Introduction

The acquisition of immune checkpoints by effector T cells renders them progressively exhausted and unable to kill tumor cells. This has led in recent years to the development of immune checkpoint blockade (ICB), which is now used to treat an increasing number of cancers. Although success stories have emerged, these strategies seem to work as monotherapies in a restricted number of patients, and some limitations have occurred with the development of acquired resistance.

Considerable attention has been paid to cancer vaccines owning to their unique advantages such as good safety profiles, antigen-specific immunological responses, and effective immune memories. Cancer vaccines are designed to bring forth the immunogenic antigens to excite patients' immune systems, particularly tumor-specific T cell responses. Accordingly, cancer vaccines and ICB can be perfectly combined to better obtain the immune responses of patients with cancers. This combination can enhance the effectiveness of destroying cancers by promoting cytotoxic T cell activity, facilitating effector T cell infiltration, and accumulating memory precursor CD8⁺ T cells.

Fig.1 Mechanisms of cancer vaccines and checkpoint blockade. (Shibata, 2019)

Preclinical and Clinical Studies Combining ICB with Vaccines

ICB in combination with cancer vaccines have been tested in some preclinical studies. Several different vaccination strategies are explored to enhance the efficacy of ICB. These include simple vaccine preparations consisting of specific peptides and proteins, as well as more complex systems, such as live attenuated vaccines and cellular vaccines.

Peptide vaccines

CTLA-4 blockade combined with peptide vaccine have been tested in phase I clinical trial, resulting in objective and durable tumor responses in melanoma patients. A multi-peptide vaccine increased the number of T cells in advanced melanoma patients when combined with PD-1 blockade in this phase I trial. Thus, early clinical data have indicated that multi-peptide vaccines combined with immune-checkpoint blockade are highly promising.

Live attenuated vaccines

Live attenuated vaccines combined with ICB have also shown great promise in human studies. Currently, a vaccine with a live-attenuated vaccine in combination with PD-L1 blockade is tested in a phase I/II trial in patients with cervical cancer or HPV-positive head and neck cancer. In summary, combination approaches with live attenuated viruses are currently tested in the clinic.

Cellular vaccines

Clinical trials combining ICB with cellular vaccines are also ongoing. Multiple pre-clinical studies, in addition, demonstrated synergistic efficacy of autologous modified tumor cellular vaccines with immunomodulatory antibodies. In a phase I/II trial with metastatic CRPC patients, treatment with cellular vaccine plus CTLA-4 blockade has demonstrated evidence of clinical benefit in treating metastatic pancreatic cancer. Thus, preclinical and early clinical data of cellular vaccines in combination with ICB are promising, warranting further clinical exploration.

Services at Creative Biolabs

The combination of vaccine therapy and ICB has yielded promising results. With our extensive experience and state-of-the-art technology, Creative Biolabs offers a series of custom services for immune checkpoints, including but not limited to:

Please do not hesitate to contact us for more detailed information.

Reference

Shibata, T.; et al. The promise of combining cancer vaccine and checkpoint blockade for treating HPV-related cancer. Cancer treatment review. 2019, 78, 8-16.

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