bispecific tces  (Paratopes)

Journal: Frontiers in Immunology

Article Title: Logic-gated and contextual control of immunotherapy for solid tumors: contrasting multi-specific T cell engagers and CAR-T cell therapies

doi: 10.3389/fimmu.2024.1490911

Figure Lengend Snippet: Architectures for OR and AND-gate bispecific CARs. (A) OR gates can respond to both TAAs either singly or together, offering an opportunity to restrict antigen escape. Two variations are shown; dual CARs which can be encoded from the same bicistronic vector, or delivered by two separate vectors, allow the use of complementary costimulation domains as shown here. Tandem CARs contain binding domains targeting two distinct antigens within the same CAR. (B) A true AND gate is only activated when both targets are present, and do not respond to cells expressing only one target. The split CAR concept places the domains that drive signal 1 (activation via the CD3z ITAM) and signal 2 (costimulation, shown here with the CD28 ITAM) on separate CARs. A more recent, and potentially more tightly controlled format are the LINK CARs, which place two effectors that lie downstream of the TCR (LAT and SLP76), on two distinct CARs, thus splitting signal 1 in two and requiring engagement of both CARs to initiate T-cell activation. Created with BioRender.com .

Article Snippet: A company called BioAtla has recently leveraged 4- to 5-fold affinity improvement at low pH for EPCAM and CD3 binders (engineered through addition of histidine switches at the CDR/antigen interface) to generate a dual Conditionally Activated Bispecific (CAB) TCE against EPCAM ( ) with a 10-fold in vitro killing window between pH 6.5 versus 7.4 ( ).

Techniques: Plasmid Preparation, Binding Assay, Expressing, Activation Assay

Journal: Cancers

Article Title: Unlocking Intracellular Oncology Targets: The Unique Role of Antibody-Based T-Cell Receptor Mimic (TCRm) Therapeutics in T-Cell Engagers (TCEs) and Antibody-Drug Conjugates (ADCs)

doi: 10.3390/cancers16223776

Figure Lengend Snippet: List of recent TCRm therapeutics in preclinical and clinical development.

Article Snippet: HIV/A2 , TCE bispecific , Preclinical , Johns Hopkins University , [ ] .

Techniques:

Journal: Cancers

Article Title: Unlocking Intracellular Oncology Targets: The Unique Role of Antibody-Based T-Cell Receptor Mimic (TCRm) Therapeutics in T-Cell Engagers (TCEs) and Antibody-Drug Conjugates (ADCs)

doi: 10.3390/cancers16223776

Figure Lengend Snippet: List of recent TCRm therapeutics in preclinical and clinical development.

Article Snippet: MAGE-A4/A2 , TCE bispecific , Phase 1 , Genentech , Clinicaltrials.gov (NCT06372574).

Techniques: