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]
Background
editProfessional 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.[5] 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
editCombinatorial 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.[6][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][2][4]
References
edit- ^ "Immutep Activities Report (ASX Announcement)" (PDF). Immutep Ltd. January 29, 2020. Retrieved February 19, 2020.
- ^ a b "LAG-3 – Regulating the Immune System | Immutep". www.immutep.com. Retrieved 2020-02-19.
- ^ W, Kratky; C, Reis e Sousa; A, Oxenius; R, Spörri (2011-10-18). "Direct Activation of Antigen-Presenting Cells Is Required for CD8+ T-cell Priming and Tumor Vaccination". Proceedings of the National Academy of Sciences of the United States of America. 108 (42): 17414–9. Bibcode:2011PNAS..10817414K. doi:10.1073/pnas.1108945108. PMC 3198339. PMID 21987815.
- ^ a b "Immutep (ASX.IMM) Presentation, Immutep TACTI-002 Clinical Results & Update Global Webcast, February 2020". www.finnewsnetwork.com.au. Retrieved 2020-03-01.
- ^ a b Hughes, Catherine E.; Benson, Robert A.; Bedaj, Marija; Maffia, Pasquale (2016). "Antigen-Presenting Cells and Antigen Presentation in Tertiary Lymphoid Organs". Frontiers in Immunology. 7: 481. doi:10.3389/fimmu.2016.00481. ISSN 1664-3224. PMC 5097899. PMID 27872626.
- ^ a b 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. doi:10.1002/med.21553. ISSN 0198-6325. PMC 6587958. PMID 30450666.
- ^ Chen, Daniel S.; Mellman, Ira (2013-07-25). "Oncology meets immunology: the cancer-immunity cycle". Immunity. 39 (1): 1–10. doi:10.1016/j.immuni.2013.07.012. ISSN 1097-4180. PMID 23890059.
- ^ "BG9588 (Anti-CD40L Antibody) to Treat Lupus Nephritis - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2020-02-19.
- ^ 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. doi:10.2217/fon-2018-0807. ISSN 1744-8301. PMID 30977393.