APC Activator
{{Short description|Type of immunotherapy}}
APC Activators (or Antigen-presenting cell activators) are a type of immunotherapy which leverages antigen-presenting cells (APCs) to drive an adaptive immune response.{{Cite news|url=https://www.immutep.com/files/content/investor/press-release/2019/2022808.pdf|title=Immutep Activities Report (ASX Announcement)|date=January 29, 2020|work=Immutep Ltd|access-date=February 19, 2020}}{{Cite web|url=https://www.immutep.com/technology/lag-3-technology.html|title=LAG-3 – Regulating the Immune System {{!}} Immutep|website=www.immutep.com|access-date=2020-02-19}}{{Cite journal|title=Direct Activation of Antigen-Presenting Cells Is Required for CD8+ T-cell Priming and Tumor Vaccination|last=W|first=Kratky|last2=C|first2=Reis e Sousa|date=2011-10-18|language=en|pmid=21987815|last3=A|first3=Oxenius|last4=R|first4=Spörri|journal = Proceedings of the National Academy of Sciences of the United States of America|volume = 108|issue = 42|pages = 17414–9|doi = 10.1073/pnas.1108945108|pmc = 3198339|bibcode = 2011PNAS..10817414K}}{{Cite web|url=https://www.finnewsnetwork.com.au/Presentations/Immutep/IMM_260220/index.html|title=Immutep (ASX.IMM) Presentation, Immutep TACTI-002 Clinical Results & Update Global Webcast, February 2020|website=www.finnewsnetwork.com.au|access-date=2020-03-01}} 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.{{Cite journal|last=Hughes|first=Catherine E.|last2=Benson|first2=Robert A.|last3=Bedaj|first3=Marija|last4=Maffia|first4=Pasquale|date=2016|title=Antigen-Presenting Cells and Antigen Presentation in Tertiary Lymphoid Organs|journal=Frontiers in Immunology|language=en|volume=7|pages=481|doi=10.3389/fimmu.2016.00481|pmid=27872626|pmc=5097899|issn=1664-3224|doi-access=free}}
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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).{{Cite journal|last=Anwar|first=Muhammad Ayaz|last2=Shah|first2=Masaud|last3=Kim|first3=Jason|last4=Choi|first4=Sangdun|date=October 21, 2018|title=Recent clinical trends in Toll‐like receptor targeting therapeutics|journal=Medicinal Research Reviews|volume=39|issue=3|pages=1053–1090|doi=10.1002/med.21553|issn=0198-6325|pmc=6587958|pmid=30450666}}
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.{{Cite journal|last=Chen|first=Daniel S.|last2=Mellman|first2=Ira|date=2013-07-25|title=Oncology meets immunology: the cancer-immunity cycle|journal=Immunity|volume=39|issue=1|pages=1–10|doi=10.1016/j.immuni.2013.07.012|issn=1097-4180|pmid=23890059|doi-access=free}} Interest in the clinical use of TLR and CD40 agonistic antibodies in immuno-oncology wavered in the past decade.{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT00001789|title=BG9588 (Anti-CD40L Antibody) to Treat Lupus Nephritis - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|language=en|access-date=2020-02-19}} 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.{{Cite journal|last=Dirix|first=Luc|last2=Triebel|first2=Frédéric|date=June 2019|title=AIPAC: a Phase IIb study of eftilagimod alpha (IMP321 or LAG-3Ig) added to weekly paclitaxel in patients with metastatic breast cancer|journal=Future Oncology (London, England)|volume=15|issue=17|pages=1963–1973|doi=10.2217/fon-2018-0807|issn=1744-8301|pmid=30977393}}
References
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