Therapy with CD7 monoclonal antibody TH‐69 is highly effective for xenografted human T‐cell ALL

Abstract

Human T-cell acute lymphocytic leukaemia (ALL) was established in athymic nude or severe combined immunodeficient (SCID) mice by injecting CEM or MOLT-16 cells. When nude mice bearing approx. 2 g of tumour were treated with a single injection of CD7 antibody TH-69, 82.6% reached complete remission within 10 d whereas 13.0% showed partial remission. Similarly, in SCID mice with advanced disease a significant prolongation of survival was seen. The therapeutic effects were dependent upon dose and affinity of the antibody. TH-69 is a high-affinity antibody (7.6 x 10(9) M-1) that rapidly induced modulation during treatment. The Fc-portion of the antibody was required for effective tumour cell killing. Complement deposition was found on tumour sections after TH-69 treatment and in part may account for tumour destruction. There was no evidence for antibody-dependent cellular cytotoxicity (ADCC). The kinetics of tumour disappearance suggested the initiation of a programmed cell death (PCD), despite the lack of significant DNA fragmentation. Unmodified high-affinity antibodies to the T-cell antigen CD7 have potential for T-cell ALL therapy.

Identification of CD7 as a Cognate of the Human K12 (SECTM1) Protein

“…It should be possible to conjugate toxins to the extracellular domain of K12 as well; these conjugates may be less immunogenic than antibody-based conjugates, or may have a longer half-life. Conjugation of the anti-CD7 antibodies with toxins may not even be required, since anti-CD7 antibodies alone have been effective anti-tumor agents in a xenografted human T cell ALL model (44). If K12-Fc has a similar effect in this model, it would be a candidate for clinical testing against T cell leukemias.…”

CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies

“…Therefore, we disrupted the CD7 gene in T cells prior to transduction by using CRISPR/Cas9. We used CRISPRScan 20 and COSMID 21 algorithms to select 2 guide RNAs (gRNA-72 and gRNA-85) targeting the CD7 gene with minimal predicted off-target effects. We chose to target exon 2 of the CD7 gene encoding the extracellular domain to reduce the probability of generating a truncated membranebound CD7 protein following nonhomologous end joining.…”

“…Three CD7-specific single-chain variable fragments derived from 3A1e, 3A1f, 19 and TH-69 20 clones of CD7-specific antibodies were created using commercial gene synthesis (Bio Basic, Inc) and cloned into a second-generation backbone CAR containing CD28 and CD3z endodomains and the C H 3 domain from IgG1 Fc as a spacer region. A truncated CD7 CAR lacking signaling endodomains was used as a control.…”

Polymorphonuclear Granulocytes Induce Antibody-Dependent Apoptosis in Human Breast Cancer Cells

“…Control Ab was Th 69 (mIgG1) against CD7 (21). FITC-labeled F(abЈ) 2 of Ab to mouse IgG were from Cappel (Cochranville, PA).…”