A First-in-Human Trial Offers Hope for CAR-T in Solid Tumors – Cancer Therapy Advisor

While chimeric antigen receptor T-cell (CAR-T) therapy has been making waves for the last few years as a novel treatment approach in cancer, the successes have remained mostly in the realm of blood cancers. This makes a first-in-human CAR-T clinical trial that targets a solid tumor growth receptor called MUC1* stand out. At the 34th Annual Meeting & Preconference Programs of the Society for Immunotherapy of Cancer, or SITC 2019, in November 2019, Minverva Biotechnologies shared an abstract offering some details behind this trial, which began in September 2019.1

Many clinical trials have tried to target the full-lengthMUC1 protein and have failed. The failures are likely due to the fact that MUC1is cleaved and released from the tumor surface, meaning any therapy that bindswith it goes too. When MUC1 is cleaved, however, the binding site for a crucialgrowth factor receptor that Minerva is calling MUC1* is revealed, said CynthiaBambdad, PhD, CEO of Minerva.

Leaving MUC1* exposed and unattended is like the pin beingpulled on the hand grenade, Dr Bamdad said. When a growth factor comes alongand binds to the MUC1* receptor, it causes the cancer cells to grow and becomeresistant to chemotherapy.

Minervas new investigational CAR-T therapy aims to swoop in and bind to the MUC1* receptor to block growth factors from accessing the MUC1 cleavage product. This binding and blocking action can, theoretically, stop a tumor from growing. The CAR-T therapy also aims to kill any mutant cancer cells in its vicinity and send out a call to the patients immune system to produce more like-minded CAR-T cells to shrink the tumor.

Its a very unique approach to MUC1, and thats why weemphasize that its different, said Matt Britz, head of business developmentat Minerva, referring to a line in the companys abstract that calls outprevious failed trials that looked only at full-length MUC1 and not the MUC1*receptor.

Up to now, CAR-T therapy has been so specifically successfulwith blood cancers because theyre malignancies of B cells, which CAR T-cellscan completely wipe out (it also can eliminate healthy B cells in the process,which can affect a patients ability to ward off infections). The patient mayget a sniffle more often, but is otherwise okay, Dr Bamdad remarked.

But this same approach doesnt work with solid tumors because they have no B-cell equivalent. Its been a challenge to find a solid tumor target that is not also present on healthy cells, which, if wiped out, could negatively impact a patients chances of survival.

Our approach is unique in that the CAR-T that we developedbinds to the part of MUC1* that is masked on healthy tissue, she said. TheCAR-T cells very selectively bind to and kill the tumor cells.

Dr Bamdad also said that MUC1*, which is expressedaberrantly in 95% of breast cancers, 83% of ovarian cancers, 78% of pancreaticcancers, and 71% of lung cancers, is the closest thing there is to a B-cellequivalent in solid tumors.

If this trial is successful, it will be a major step forward toward CAR-T cures for solid-tumor cancers, which make up 93% of all cancers, Dr Bamdad added.

Britz said that an obstacle in getting CAR-T therapy to gomainstream is that its still seen as being prohibitively expensive but heremains hopeful that as there are more successes in trials, there will be aparallel effort to bring the cost down. I think were in a paradigm shift inthe way that cancer is going to be treated, he said.

Reference

Bamdad C, Stewart A, Huang P, Smagghe B, Moe S, Swanson T,Jeon T, Page D, Mathavan K, Grant T, Herrup R. Poster presented at: the 34thAnnual Meeting & Preconference Programs (SITC 2019); November 610, 2019;National Harbor, MD. Abstract P150.

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A First-in-Human Trial Offers Hope for CAR-T in Solid Tumors - Cancer Therapy Advisor