CAR-CD44v6 / Ospedale San Raffaele, AGC Biologics - LARVOL DELTA

CD44v6 CAR-T Cells Target DNMT3A-Mutant AML: Synergistic Enhancement by Decitabine. (PubMed, Curr Med Sci) - "CD44v6 is a promising CAR-T-cell therapy target in AML patients with DNMT3A mutations. Notably, treatment with decitabine resulted in increased CD44v6 expression on the cell surface of DNMT3A-mutant AML cells. This increase in CD44v6 expression facilitates improved recognition and targeting by CD44v6 CAR-T cells."

IO biomarker • Journal • Acute Myelogenous Leukemia • Gene Therapies • Hematological Malignancies • Leukemia • Oncology • ANXA5 • DNMT3A

CD44v6-Targeted CAR-T Immunotherapy to reduce metastatic evolution in Thyroid Cancer (EACR 2025) - "We evaluated CD44v6 CAR-T cells anti tumor activity, transducing isolated T-lymphocytes with lentivirus expressing human CD44v6-CAR and co-cultured them with TC cells in vitro at different effector-to-target (E:T) ratios... Our findings highlight CD44v6's key role in TC progression, suggesting that CAR-T therapy could be effective. However, reprogramming of CD44v6- cells challenges treatment efficacy. Identifying the molecular mechanisms driving this switch could open avenues for combination therapies."

IO biomarker • Metastases • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF • CTNNB1 • NRAS

Cytotoxic and antitumoral effect of an anti-CD44v6 CAR-T against gastric cancer (AACR 2025) - "We have successfully developed CAR T cells possessing medium affinity against CD44v6 and confirmed CAR-specific killing of CD44v6 positive gastric cancer cells."

IO biomarker • Gastric Cancer • Oncology • Solid Tumor • CD69 • PD-1

Single-cell analysis of the survival mechanisms of fratricidal CAR-T targeting of T cell malignancies. (PubMed, Mol Ther Nucleic Acids) - "We performed single-cell transcriptome profiling to investigate the fratricidal CAR-T products (CD26 CAR-Ts and CD44v6 CAR-Ts) targeting T cells, taking CD19 CAR-Ts targeting B cells from the same donor as a control...Single-cell regulatory network analysis and suppression experiments revealed that exhaustion mediated by critical regulatory factors may contribute to fratricidal CAR-T cell survival. Together, these data provide valuable and first-time insights into the survival of fratricidal CAR-T cells."

IO biomarker • Journal • Oncology • DPP4

Demethylating therapy increases cytotoxicity of CD44v6 CAR-T cells against acute myeloid leukemia. (PubMed, Front Immunol) - "Hypomethylating agents (HAMs) decitabine (Dec) and azacitidine (Aza) have been widely used to treat AML. The combination of Dec or Aza pretreated CD44v6 CAR-T with pretreated AML cells demonstrated the most potent anti-tumor ability against AML. Dec or Aza in combination with CD44v6 CAR-T cells is a promising combination therapy for AML patients."

CAR T-Cell Therapy • IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • DNMT3A • FLT3

CD44v6 chimeric antigen receptor T cell specificity towards AML with FLT3 or DNMT3A mutations. (PubMed, Clin Transl Med) - "CD44v6 CAR-T cells were constructed by transfecting T cells with lentivirus containing CD44v6 CAR...Furthermore, we found that FLT3 or DNMT3A mutations induced CD44v6 overexpression by downregulating the CpG methylation of CD44 promoter. Collectively, CD44v6 is a promising target of CAR-T for AML patients with FLT3 or DNMT3A mutations."

CAR T-Cell Therapy • IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD44 • DNMT3A • FLT3

Study of CAR T-cell Therapy in Acute Myeloid Leukemia and Multiple Myeloma (clinicaltrials.gov) - P1/2; N=8; Terminated; Sponsor: AGC Biologics S.p.A.; N=58 ➔ 8; Trial completion date: Jun 2023 ➔ Jun 2021; Recruiting ➔ Terminated; Trial primary completion date: Jun 2023 ➔ Jun 2021; Inability to close the study in a clinically relevant time frame

CAR T-Cell Therapy • Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • CD44 • FLT3

Developing a Safer Anti-CD44v6 Chimeric Antigen Receptor T Cell Against Hematological Cancers By Mitigating on-Target Off-Tumor Toxicity (ASH 2021) - "We have developed a second generation, anti-CD44v6 CAR T cell (CD44v6CAR) that mediates potent cytotoxic and effector function against AML and MM in-vitro...Selective inhibition of matrix metalloproteinase-2 in the multiple myeloma-bone microenvironment. Oncotarget 8 , 41827-41840, (2017)."

CAR T-Cell Therapy • IO biomarker • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Cognitive Disorders • Head and Neck Cancer • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD44 • GLI2 • MMP2