Multispecific antibody shows promise in B cell lymphoma

Monoclonal antibodies

A multispecific antibody candidate for B cell lymphoma preferentially engaged CD47 in presence of co-engagement of CD20 and CD19, in preclinical investigations.

One dose of Nutcracker Therapeutics’ NTX-472 in vivo rapidly depleted B cells with no detectable binding to red blood cells.

The results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Monoclonal antibody immunotherapies can provide an effective treatment for B cell lymphoma. However, by only targeting a single tumour antigen, such as CD19 or CD20, these treatments can place selective pressures on tumours, with cancer cells often down-regulating the expression of those specific antigens to become cold tumours, invisible to the immune system.

Multispecific antibodies may be able to mitigate these effects with improved specificity to several antigens at once.

Nutcracker Therapeutics’ scientists engineered a panel of molecules simultaneously targeting CD20, CD19 and CD47 to compare them to existing monoclonal antibody immunotherapies for B cell lymphoma, including rituximab (monospecific anti-CD20) and tafasitamab (monospecific anti-CD19).

Of these molecules, the team identified one which had improved tumour killing and B cell depletion in vitro, which became the NTX-472 programme.

“We’re proud to be one of the first RNA therapeutics companies to engineer a multispecific antibody,” said Chief Scientific Officer Samuel Deutsch. “We plan to further develop NTX-472 as a trispecific immunotherapy with a differentiated therapeutic and safety profile.” Read the DDW interview with Sam Deutsch.

Previously Nutcracker Therapeutics presented preclinical data on NTX-471, an mRNA therapeutic candidate that is being developed to target CD47. Unlike the multispecific approach employed by NTX-472, NTX-471 encodes for a multivalent (octavalent) antibody to achieve high specificity via avidity for target cancer cells.

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