Inhibiting the CTLA-4 Pathway May Lead to T-Cell Activation and Proliferation and the Generation of Memory T Cells1-5

CTLA-4 is a co-inhibitory receptor

The major histocompatibility complex (MHC) on tumor cells must also present antigens to T-cell receptors to activate T cells.6

 

The CTLA-4 pathway acts to downregulate an immune response by binding to CD80 (B7.1) or CD861-3

Inhibiting the CTLA-4 pathway leads to T-cell activation and proliferation and may help generate memory T cells1-5

Video: “CTLA-4 Inhibition”Video: “CTLA-4 Inhibition”
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Tremelimumab (Anti–CTLA-4 Antibody)

Tremelimumab is an investigational, selective human IgG2 mAb inhibitor of CTLA-4.7,8

Tremelimumab promotes T-cell activity through CTLA-4 inhibition, but does not deplete regulatory T cells.7

Tremelimumab is being clinically investigated as a combination therapy for the potential treatment of cancer.9

When used in combination with an anti–PD-L1 agent, tremelimumab may have the potential to boost the biological and clinical effect of PD-L1 inhibition.9

As cancer immunotherapy, tremelimumab may have the potential to provide treatment to a different population of cancer patients. This includes working in combination with durvalumab (MEDI4736), where both therapies may have enhanced activity compared to each one being used on its own.9

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References: 1. Intlekofer AM, Thompson CB. At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol. 2013;94(1):25-39. 2. Gardner D, Jeffery LE, Sansom DM. Understanding the CD28/CTLA-4 (CD152) pathway and its implications for costimulatory blockade. Am J Transplant. 2014;14(9):1985-1991. 3. Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol. 2002;3(7):611-618. 4. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450-461. 5. Pedicord VA, Montalvo W, Leiner IM, Allison JP. Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance. Proc Natl Acad Sci USA. 2011;108(1):266-271. 6. Delves PJ, Martin SJ, Burton DR, Roitt IM. Roitt's Essential Immunology. 13th ed. Chichester, West Sussex, UK: Wiley-Blackwell; 2017. 7. Tarhini AA. Tremelimumab: a review of development to date in solid tumors. Immunotherapy. 2013;5(3):215-229. 8. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264. 9. Antonia S, Goldberg SB, Balmanoukian A, et al. Safety and antitumor activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016;17(3):299-308.

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