Multiple patient-specific tumor-associated antigens presented on peptide-MHC complexes recognized by polyclonal TCRs on LM103 TILs (LM103 target antigens)

The target consists of a diverse array of patient-specific tumor-associated antigens (TAAs) and neoantigens presented on peptide-MHC (pMHC) complexes. These antigens are uniquely recognized by the polyclonal T-cell receptors (TCRs) found on LM103, an autologous tumor-infiltrating lymphocyte (TIL) therapy developed by Suzhou BlueHorse Therapeutics. Unlike traditional targeted therapies that focus on a single protein, this target represents a broad spectrum of mutations and overexpressed proteins specific to an individual's tumor, which helps overcome tumor heterogeneity and prevents antigen escape. Recognition of these pMHC complexes by LM103 TILs triggers a potent immune response, characterized by the release of cytotoxic granules like perforin and granzyme B to induce cancer cell death. This therapeutic approach is primarily investigated for advanced solid tumors, including metastatic melanoma, cervical cancer, and non-small cell lung cancer. Clinical studies have shown that the diversity and persistence of TCR clones recognizing these antigens are critical for achieving durable objective responses in patients who have failed standard therapies. The safety profile of targeting these antigens is generally manageable, though it is often complicated by the intensive lymphodepletion and interleukin-2 (IL-2) regimens required for TIL therapy.

Other names

Patient-specific neoantigensTumor-associated antigens (TAAs)pMHC complexesLM103 targetsTumor-infiltrating lymphocyte targets

LM103 is an autologous tumor-infiltrating lymphocyte (TIL) therapy that utilizes polyclonal T-cell receptors (TCRs) to recognize a broad spectrum of patient-specific tumor-associated antigens (TAAs) and neoantigens presented on major histocompatibility complex (MHC) molecules. Upon binding to these peptide-MHC (pMHC) complexes, the TILs are activated and execute cytotoxic functions by releasing perforin and granzymes, as well as secreting pro-inflammatory cytokines like IFN-gamma and TNF-alpha, leading to targeted tumor cell apoptosis.