Autologous HLA-A*11:01 KRASG12V-specific TCR-expressing CD8- and CD4-positive T lymphocytes AFNT-211

{
  "id": "MLC-T-ONC-011648",
  "term": "Autologous HLA-A*11:01 KRASG12V-specific TCR-expressing CD8- and CD4-positive T lymphocytes AFNT-211",
  "field": "Oncology and biomedicine",
  "definition": "A preparation of autologous HLA class I histocompatibility antigen A*11:01 (HLA-A1101)-positive CD8- and CD4-positive T lymphocytes that have been transduced with a lentiviral vector expressing a HLA-A*11:01-restricted T-cell receptor (TCR) that recognizes the glycine to valine point mutation at position 12 (G12V) variant of Kirsten rat sarcoma (K-RAS; KRAS), and enhanced with the wildtype CD8alpha/beta (CD8a/b) coreceptor, and a FAS-41BB switch receptor, and subsequently expanded ex vivo, with potential immunomodulating and antineoplastic activities. When reintroduced into the patient, the autologous HLA-A*11:01 KRASG12V-specific TCR-expressing CD8- and CD4-positive T lymphocytes AFNT-211 specifically recognize and bind to KRASG12V expressed on tumor cells, which results in both cytokine secretion and cell lysis in tumor cells overexpressing KRASG12V. K-RAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. The KRASG12V mutation is overexpressed in a variety of cancer cell types. Mutation of K-RAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis. CD8a/b coreceptor and a FAS-41BB switch receptor improve T-cell persistence. The introduction of the CD8a/b coreceptor enables a coordinated CD4+/CD8+ T-cell response and enables CD4+ T-cell recognition of KRASG12V and enhances cytotoxicity. FAS-41BB converts the FAS ligand (FASL) tumor microenvironment (TME) death signal into a costimulatory signal through 41BB activation, thereby enhancing the durability of the anti-tumor immune response against FASL-expressing tumor cells.",
  "synonyms": [
    "autologous engineered TCR T cells AFNT-211",
    "autologous FAS-41BB-enhanced HLA-A*11:01 KRASG12V-specific TCR-T cells AFNT-211"
  ],
  "references": [
    "National Cancer Institute Thesaurus"
  ],
  "url": "https://mlchart.com/terminology/oncology/autologous-hla-a-11-01-krasg12v-specific-tcr-expressing-cd8-and-cd4-positive-t/"
}