Elsevier

Leukemia Research

Volume 108, September 2021, 106626
Leukemia Research

An antibody-drug conjugate with intracellular drug release properties showing specific cytotoxicity against CD7-positive cells

https://doi.org/10.1016/j.leukres.2021.106626Get rights and content
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open access

Highlights

  • The CD7 surface protein is highly expressed on T cell acute leukaemias.

  • CD7 bound by antibody is rapidly processed and internalised into cells.

  • The novel antibody-drug conjugate kills CD7 expressing leukaemias.

  • The ADC linker is only cleaved in cells.

  • CD7 ADCs are a treatment option for CD7-expressing cancers.

Abstract

Refractory T cell acute leukaemias that no longer respond to treatment would benefit from new modalities that target T cell-specific surface proteins. T cell associated surface proteins (the surfaceome) offer possible therapy targets to reduce tumour burden but also target the leukaemia-initiating cells from which tumours recur. Recent studies of the T cell leukaemia surfaceome confirmed that CD7 is highly expressed in overt disease. We have used an anti-CD7 antibody drug conjugate (ADC) to show that the binding of antibody to surface CD7 protein results in rapid internalization of the antigen together with the ADC. As a consequence, cell killing was observed via induction of apoptosis and was dependent on cell surface CD7. The in vitro cytotoxic activity (EC50) of the anti-CD7 ADC on T cell acute leukaemia (T-ALL) cells Jurkat and KOPT-K1 was found to be in the range of 5−8 ng/mL. In a pre-clinical xenograft model of human tumour growth expressing CD7 antigen, growth was curtailed by a single dose of ADC. The data indicate that CD7 targeting ADCs may be developed into an important second stage therapy for T cell acute leukaemia, for refractory CD7-positive leukaemias and for subsets of acute myeloid leukaemia (AML) expressing CD7.

Keywords

Leukaemia
CD7
ADC
Antibody
T cell leukaemia
Intracellular drug delivery

Cited by (0)

1

Jing Zhang: UCB Pharma, 216 Bath Road, Slough, SL1 3WE, UK.

2

Arvind Jain: Sun Pharma Advanced Research Company Ltd., Sun Pharma Road, Tandalja, Vadodara- 390012, India.

3

Sabine Milhas: Vertex Pharmaceuticals, 88 Jubilee Avenue, Milton Park, OX14 4RW, UK.