Combination of Immune Checkpoint Therapy with Chemotherapy

Immune checkpoint therapy has emerged as a welcome and potent addition to the current arsenal of anticancer treatment. Presently, some immune checkpoint inhibitors (ICIs) as single-agent immunotherapy has limited efficacy. Against this background, a logical approach would be using a combination of drugs to target a broader subset of tumor cells. In this respect, chemotherapy appears to assist ICI treatment by releasing neoantigens or reshaping the TME by depleting Tregs and MDSCs.

Combining chemotherapy and ICI has a proven synergistic effect since chemotherapy aids in fast tumor regression and reduces tumor burden. At the same time, ICI may prolong this effect inducing a long-lasting anti-tumor response. Preclinical data suggest that chemotherapy may enhance the immune response to ICI through multiple mechanisms, including inhibiting the immunosuppressive machinery of tumor cells, increasing tumor antigen exposure and DNA damage, and facilitating the penetration of immunotherapy agents. Thus, the non-overlapping toxicity profiles of ICI and chemotherapy render them good candidates for combination strategies.

Fig.1 Immunomodulatory effects of chemotherapy. (Heinhuis, 2019)

Clinical Studies Combining ICB and Chemotherapy

Various studies investigating combination therapy with chemotherapy and ICIs have been carried out. Both in vivo and clinical studies are showing promising results.

• Recently, a phase III clinical trial in small cell lung carcinoma (SCLC) patients, combined PD-L1 blockade with a chemotherapy regimen, demonstrated impressive results. It has been shown a significant survival benefit of the combinations when compared to chemotherapy alone. Thus, FDA has received the application of CTLA-4 blockade plus chemotherapy as the first-line.
• Concerning the clinical application, chemotherapy combined with anti-CTLA-4 was first tested in metastatic melanoma patients. A phase II study showed that more patients responded to chemotherapy plus anti-CTLA-4 when compared to anti-CTLA-4 alone. A phase III study demonstrated that this combination slightly increased the OS compared to chemotherapy alone.
• An agonistic antibody to CD40 was tested in combination with chemotherapy in patients with advanced pancreatic cancer. The promising activity was shown, which was dependent on the tumor-infiltrating macrophages. Another trial with the same agent in combination with other chemotherapy in patients with advanced solid tumors demonstrated evidence of immune activation and safety.

Fig.2 Principal effects of ICI-based immunotherapy combined with chemotherapy on the host immune system. (Leonetti, 2019)

Services at Creative Biolabs

Combining state-of-the-art technology with personal service and attention, Creative Biolabs offers a series of custom services for immune checkpoints, including but not limited to:

• Immune Checkpoint Antibody Development
• Immune Checkpoint Targeted Small Molecule Drug Development
• Immune Checkpoint Assays
• Custom Immune Checkpoint Protein Development
• Immune Checkpoint Targeted Peptide Development
• Preclinical Research for Immune Checkpoint Drugs

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

References

1. Heinhuis, K. M.; et al. Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors. Annals of Oncology. 2019, 30(2), 219-235.
2. Leonetti, A.; et al. Molecular basis and rationale for combining immune checkpoint inhibitors with chemotherapy in non-small cell lung cancer. Drug Resistance Updates. 2019, 46, 100644.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.