CD72 nanoCAR T / University of California - LARVOL DELTA

Anti-CD72 nanobody-based CAR-T affinity maturation leads to improved in vitro efficacy versus low antigen density lymphoma models, but limited benefit in vivo (AACR 2025) - "CD72 is a potential second line antigen post-CD19 relapse in B-cell malignancies. We found that affinity maturation did not demonstrably improve CD72 nanoCAR efficacy. Our results support findings demonstrated for scFv-based CARs, that moderate affinity for surface antigen may lead to optimal CAR performance in vivo, even when nanobodies are used as the recognition element."

IO biomarker • Preclinical • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CD22 • TCF19

Humanized Nanobody Anti-CD72 CAR-T Cells Efficiently Eliminate B-Cell Malignancies Via Improved Affinity for CD72 but Induce Persistent Antigen Downregulation In Vivo (ASH 2022) - "We have developed a new, humanized anti-CD72 cellular therapy known as H24 nanoCARs. Humanizing the framework regions, while keeping the complementary determining regions (CDRs) identical to NbD4, was intended to reduce immunogenicity. We were surprised that eight amino acid substitutions in the framework regions, with no changes to CDRs, improved antitumor efficacy and binding affinity for CD72."

CAR T-Cell Therapy • IO biomarker • Preclinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • CD22 • CD8 • IFNG • IL2

CD72 Nanobody-Based CAR-T Cells Have Potent Anti-Tumor Efficacy in B Cell Malignancies (ASH 2021) - "Our results demonstrate that our fully synthetic CD72 nanoCARs can effectively eliminate CD72-expressing B-cell malignancy models despite low nanobody binding affinity. Humanized NbD4 variants may serve as clinical candidates with even further reduction in possible immunogenicity of the llama amino acid framework. Alterations to the CAR backbone have a major impact on anti-tumor efficacy and phenotypes of our synthetic nanobodies."

CAR T-Cell Therapy • Clinical • IO biomarker • Bone Marrow Transplantation • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Transplantation • CD19 • CD22 • CD4 • CD8 • KMT2A