Antibody strategy to augment versatile immune cells sparks investment in French biotech
A small fraction of versatile immune cells — prized for their ability to hack the tumor microenvironment — are shaping up to be the next wave of immunotherapies. These gamma delta T cells, in contrast to their popular alpha beta counterparts harnessed by CAR-T therapies, do not rely on specific antigens but kill when presented with generic expressions of infection or disease.
Most players in the field are working on ways to improve existing cell therapies, by shoring up efficacy, limiting toxicity, making the technology more accessible with “off-the-shelf” approaches versus the existing complex autologous model, and expanding it to other cancer types beyond hematological malignancies by enlisting lymphocytes such as gamma delta T cells. These efforts are not trying to reinvent the CAR-T wheel, but indeed smoothen it so it moves faster, better and stronger for a broader group of cancer patients.
The interest in gamma delta T cells is driven by the understanding that their presence in the tumor microenvironment is typically linked to a better prognosis. But instead of extracting gamma delta T cells to enhance their activity, French biotech ImCheck Therapeutics has devised an approach that relies on butyrophilin (BTN) molecules — which are named after the eponymous protein in cow’s milk — to boost the action of certain gamma delta T cells.
“The beauty of it is that we’re using the patient’s internal gamma delta T cells, are not taking them out, but are using a monoclonal (antibody) that can be administered once every three weeks quite simply over 30 minutes in an infusion,” Paul Frohna, ImCheck’s chief medical officer, noted in an interview with Endpoints News.
“What we’re doing is just essentially harnessing that potential that they (gamma delta T cells) innately possess and amplifying it to a point where they really become active in searching out and destroying the cancer cells.”
On Wednesday, the company unveiled it had secured $53 million in Series B financing, bringing the total capital raised in 2.5 years to nearly $80 million. The money will be used to shepherd its lead immuno-oncology program, ICT01, into the clinic next year.
The therapy is engineered to work in two ways — to drive the gamma delta T cells circulating in the bloodstream to look for infected cells or tumors, while activating the gamma delta T cells that are already within the tumor microenvironment, Frohna said.
The raft of drug developers — including GammaDelta Therapeutics and its new spinoff Adaptate, Regeneron-backed Adicet Bio, Netherlands-based Gadeta, and Scotland’s TC BioPharm — keen on gamma delta T cells is growing. But ImCheck is convinced its approach, though early in the testing phase, has tangible advantages over the crop.
There are other scientists cognizant of the impact of BTNs on gamma delta T cells, but ImCheck is the only company employing the monoclonal antibody approach, chief Pierre d’Epenoux suggested.
Despite the profound clinical responses induced by the infusion of genetically-modified alpha beta T cells packaged as CAR-T therapies, the existing approach is riddled with limitations. They only work in blood cancers, don’t work for a number of patients, toxicity is an issue, are time-consuming to produce, and the manufacturing apparatus required is immense. Sales of the pioneering CAR-Ts — Novartis’ Kymriah and Gilead’s Yescarta — which can cost up to $1 million per patient, have underwhelmed as a result.
Meanwhile, monoclonal antibodies are familiar technology and are relatively easier to engineer, produce and maneuver through the regulatory system, d’Epenoux said.
The ImCheck injection was co-led by the venture capital arm of Pfizer, and Bpifrance — with participation from new investors including Wellington Partners, Agent Capital and Alexandria Venture Investments, as well as existing backers such as Life Sciences Partners, Gimv, Idinvest Partners, Kurma Partners, and Boehringer Ingelheim Venture Fund.