APC Activator explained

APC Activators (or Antigen-presenting cell activators) are a type of immunotherapy which leverages antigen-presenting cells (APCs) to drive an adaptive immune response.[1] [2] [3] [4] APC Activators are agonists to APC surface-expressed ligands that, when bound, induce the maturation and activation of APCs. Professional antigen-presenting cells – including dendritic cells, macrophages, and B cells – serve an indispensable role in the adaptive immune response through their unique ability to phagocytose, digest, and present exogenous (circulating) antigens to T cells, facilitating antigen-specific immune responses.[5] __TOC__

Background

Professional APCs express MHC class II and CD40 molecules as surface receptors, and can be activated through direct interactions with T cells expressing these receptors' corresponding ligands, LAG-3 and CD40-L, respectively. A third class of receptors that can activate APCs are called toll-like receptors (TLRs); these receptors bind foreign ligands which are structurally conserved molecules from microbes, called pathogen-associated molecular patterns (PAMPs).[6]

Therapeutic potential

Combinatorial approaches that target multiple aspects of the cancer immunity cycle, including APC activation, are promising strategies for the treatment of diseases, including numerous types of cancer.[7] Interest in the clinical use of TLR and CD40 agonistic antibodies in immuno-oncology wavered in the past decade.[8] The APC Activator IMP321 (Eftilagimod alpha), a soluble LAG-3 fusion protein, is currently undergoing clinical trials in combination with chemotherapy (paclitaxel), or immune checkpoint inhibitors, including the PD-1 monoclonal antibody pembrolizumab, to accelerate the adaptive immune response in several tumor indications.[9]

Notes and References

  1. News: Immutep Activities Report (ASX Announcement). January 29, 2020. Immutep Ltd. February 19, 2020.
  2. Web site: LAG-3 – Regulating the Immune System Immutep. www.immutep.com. 2020-02-19.
  3. Direct Activation of Antigen-Presenting Cells Is Required for CD8+ T-cell Priming and Tumor Vaccination. W. Kratky. C. Reis e Sousa. 2011-10-18. en. 21987815. A. Oxenius. R. Spörri. Proceedings of the National Academy of Sciences of the United States of America. 108. 42. 17414–9. 10.1073/pnas.1108945108. 3198339. 2011PNAS..10817414K.
  4. Web site: Immutep (ASX.IMM) Presentation, Immutep TACTI-002 Clinical Results & Update Global Webcast, February 2020. www.finnewsnetwork.com.au. 2020-03-01.
  5. Hughes. Catherine E.. Benson. Robert A.. Bedaj. Marija. Maffia. Pasquale. 2016. Antigen-Presenting Cells and Antigen Presentation in Tertiary Lymphoid Organs. Frontiers in Immunology. en. 7. 481. 10.3389/fimmu.2016.00481. 27872626. 5097899. 1664-3224. free.
  6. Anwar. Muhammad Ayaz. Shah. Masaud. Kim. Jason. Choi. Sangdun. October 21, 2018. Recent clinical trends in Toll‐like receptor targeting therapeutics. Medicinal Research Reviews. 39. 3. 1053–1090. 10.1002/med.21553. 0198-6325. 6587958. 30450666.
  7. Chen. Daniel S.. Mellman. Ira. 2013-07-25. Oncology meets immunology: the cancer-immunity cycle. Immunity. 39. 1. 1–10. 10.1016/j.immuni.2013.07.012. 1097-4180. 23890059. free.
  8. Web site: BG9588 (Anti-CD40L Antibody) to Treat Lupus Nephritis - Full Text View - ClinicalTrials.gov. clinicaltrials.gov. en. 2020-02-19.
  9. Dirix. Luc. Triebel. Frédéric. June 2019. AIPAC: a Phase IIb study of eftilagimod alpha (IMP321 or LAG-3Ig) added to weekly paclitaxel in patients with metastatic breast cancer. Future Oncology (London, England). 15. 17. 1963–1973. 10.2217/fon-2018-0807. 1744-8301. 30977393.

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