#immunotherapy targeting peptide-#HLA complexes encompass soluble T cell receptors #TCR and #antibodies, such as Immunocore's recently approved tebentafusp, but also #Tcells engineered to express a #TCR, through adoptive cell therapy #act. This recent review guides us through the clinical experience with #TCR therapy, which (even though limited) performs better in solid tumors as compared to CAR therapy. Only a couple of #targets have been evaluated essentially consisting of: - #melanoma-specific antigens like MART1, gp100, tyrosinase and other cell type-specific antigens like CEA, mesothelin and AFP - Cancer-germline antigens such as NY-ESO-1, MAGEA1, MAGEA3, MAGEA4, PRAME and more recently KK-LC-1/CT83 - over-expressed WT1, usually in AML - #virus epitopes - #neoantigen (again more recently) mostly against RAS and TP53 While new generation #Tcell engineering offers hope for improved efficacy, most of the targets are not ideal and difficult to study. The cancer-testis antigens, e.g. are widely expressed in many cancers, but at variable degree and trial design is complicated by the lack of effective ways to quantitate target expression on cancer cells. In my opinion, innovative #precisionmedicine is essential for improved #clinical #efficacy.
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Check out our latest publication in #NatureCancer. We have combined the CD80 ectodomain with the 4-1BB cytoplasmic domain to design a synthetic dual co-stimulatory molecule. This design function both as a ligand and a receptor to provide critical CD28 and 4-1BB signaling to T cells, while serving as a switch receptor when interacting with the inhibitory molecule CTLA4. This antigen-agnostic receptor boosted the antitumor response across different targeted T cell therapies including HLA-independent TCR (HIT) receptor, TCR-engineered T cells, and tumor-infiltrating lymphocytes (TILs). Kudos to the whole team and special thanks to our collaborators Taha Merghoub, Jedd Wolchok and Andrew Chow #Immunotherapy, #CARTCells, #TCR, #TILs
Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies - Nature Cancer
nature.com
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Want to learn more about ADCs? This is a good read!
Reimagining cancer care that enhances quality of life, reduces pain and suffering and extend lives for communities around the world | Columbia Business School
Yet another ADC review. The authors mention that ADCs selectively target cancer cells with a toxic payload via antibody binding to specific tumor antigens, and spare non-malignant tissues. The reality is that ADCs are not that extremely selective and only 2-5% reaches the tumor. ADCs do not only work through antigen binding but also has bystander effects. Plenty of data would suggest that ADCs have off-site toxicity that may be categorized as “on-target” or “off-target.” But these characteristics allow for their impressive anti tumor activity, leading to prolonged survival for many patients! #antibodydrugconjugates #adc #efficacy #toxicity
Antibody–Drug Conjugates: Ushering in a New Era of Cancer Therapy
mdpi.com
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A newly published paper from Jennifer Cochran and colleagues offers structural insights into the interplay between LAG-3 homodimerization, ligand binding, and function. LAG-3 is the target of relatlimab, a component of the approved product Opdualag (relatlimab + nivolumab combo), as well as over 20 antibody therapeutics currently in clinical studies. From the abstract: Here, we present a high-resolution structure of glycosylated mouse LAG-3 ectodomain, identifying that cis-homodimerization, mediated through a network of hydrophobic residues within domain 2 (D2), is critically required for LAG-3 function. Additionally, we found a previously unidentified key protein-glycan interaction in the dimer interface that affects the spatial orientation of the neighboring D1 domain. Mutation of LAG-3 D2 residues reduced dimer formation, dramatically abolished LAG-3 binding to both MHCII and FGL1 ligands, and consequentially inhibited the role of LAG-3 in suppressing T cell responses. Intriguingly, we showed that antibodies directed against D1, D2, and D3 domains are all capable of blocking LAG-3 dimer formation and MHCII and FGL-1 ligand binding, suggesting a potential allosteric model of LAG-3 function tightly regulated by dimerization. Furthermore, our work reveals unique epitopes, in addition to D1, that can be targeted for immunotherapy of cancer and other human diseases. #mabs https://lnkd.in/eUGBtHNj
Structural insights reveal interplay between LAG-3 homodimerization, ligand binding, and function - PubMed
pubmed.ncbi.nlm.nih.gov
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Biomedical Scientist/ Engineer in nucleic acid gene therapy, biomaterials, cell therapy, 3D cell encapsulation and medical device | Creator in Blog, YouTube video, Facebook Fanpage | Scientific Education | Leadership
Dr. Mitchell’s group published an innovative research on in vivo CAR-T therapy. Chimeric antigen receptor (CAR) T cell therapy has made significant strides in treating blood cancers but faces challenges due to its complex and labor-intensive production process. Traditionally, this involves a multi-step procedure starting with leukapheresis, followed by ex vivo activation of T cells using antibodies attached to magnetic beads, and finally, introducing the CAR construct. The process is complicated further by the need to remove the beads before the cells can be used clinically. To simplify this, the research introduces activating lipid nanoparticles (aLNPs) that mimic the role of antigen-presenting cells, enabling a combined one-step activation and transfection of T cells. This approach has been validated in a mouse model, showing that mRNA CAR T cells produced via aLNPs can effectively reduce tumor sizes, suggesting a promising method for quicker and potentially more cost-effective CAR T cell production. #CARTherapySimplified #NextGenCAR-T #CancerTreatmentInnovation #LipidNanoparticles #aLNPRevolution #TCellActivation #HematologyOncology #BiotechBreakthroughs #ClinicalSuccess #TherapeuticAdvancements #InnovativeCARTTherapy
Antigen Presenting Cell Mimetic Lipid Nanoparticles for Rapid mRNA CAR T Cell Cancer Immunotherapy
onlinelibrary.wiley.com
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Assessing DDX53 as a potential early esophageal cancer antigen - News Medical: ... big data setting to evaluate TCR CDR3-cancer testis antigen (CTA) chemical complementarities. "To better understand the potential positive and ... #bigdata #cdo #cto
Assessing DDX53 as a potential early esophageal cancer antigen
news-medical.net
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Antibody Therapeutics (2022 CiteScore: 6.4), the official journal of our society, now calls for papers regarding Cell Therapies and Cell Engagers against Cancer. We encourage the submissions of original research and review articles covering a broad range of topics in the fields of cell therapy and cell engagers. This includes TILs, TCR-T, CAR-T, natural killer (NK) cells, and other immune cell-based therapies. We also invite contributions on all formats of cell engagers that redirect T cells, NK cells, macrophages, and other immune cells. The two guest editors of this special collection are Dr. Baomei Wang, Principal Scientific Researcher at Genentech and Dr. Chengbin Wu, CEO and Founder of EpimAb Biotherapeutics, Inc.. #antibodies #antibody #antibodytherapeutics #mabs #mab #antibodydiscovery #biologics #celltherapy #celltherapies #cellengagers #bispecific #bispecificantibody
Call for Papers: Cell Therapies and Cell Engagers against Cancer
academic.oup.com
