CAR T-Cell Therapy, MB-105, Shows Promise in Metastatic CRPC Patient in Phase 1 Trial

CAR T-Cell Therapy, MB-105, Shows Promise in Metastatic CRPC Patient in Phase 1 Trial
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A heavily pretreated patient with metastatic castration-resistant prostate cancer (mCRPC) showed significant benefits, including a 94% decrease in the levels of the prostate-specific antigen (PSA) biomarker, one month after receiving MB-105 in a Phase 1 clinical trial.

The promising initial data from Mustang Bio‘s investigational CAR T-cell therapy were shared at the 27th Annual Prostate Cancer Foundation Scientific Retreat, which was held virtually from Oct. 20–23.

Tanya Dorff, MD, an oncologist at City of Hope National Medical Center in California, and the trial’s principal investigator gave the presentation, titled “Clinical Development of PSCA-Targeted CAR T Cells for Advanced Prostate Cancer.”

The trial (NCT03873805) is actively recruiting adult mCRPC patients, who progressed while receiving a second-generation androgen receptor inhibitor, at the City of Hope center in Duarte. Additional data are expected by 2021.

“We are encouraged by the initial data presented by City of Hope from the ongoing Phase 1 trial of Mustang’s CAR T cell therapy MB-105,” Manuel Litchman, MD, president and CEO of Mustang, said in a press release.

mCRPC refers to a form of prostate cancer that is both metastatic, meaning it has spread to distant locations, and castration-resistant, which means that the tumor continues to grow even when the amount of testosterone is reduced to very low levels.

Mustang’s MB-105, initially developed at City of Hope laboratories, is a type of immunotherapy with the potential to treat prostate, pancreatic, gastric, and bladder cancers by directly attacking tumor cells.

MB-105 consists of a patient’s own T-cells, immune system cells with the ability to fight cancer, that have been genetically engineered in the lab to more efficiently attack tumor cells.

These engineered cells, called CAR T-cells, are specifically modified to produce a man-made chimeric antigen receptor, or CAR, that helps them recognize and kill cells containing the prostate stem cell antigen (PSCA) protein, without harming healthy cells.

The PSCA protein is found at higher levels in cancer cells, with limited expression in normal tissues, and is found on the surface of the cells, making it an ideal target for this immunotherapy approach.

Following the genetic engineering step of the CAR T-cell process, these cells are allowed to grow under laboratory conditions before being administered as a therapy via blood infusion. Some form of immunosuppression, such as chemotherapy, is typically administered with CAR T-cells, to reduce the likelihood of an immune response to the modified T-cells.

Researchers launched a Phase 1 clinical trial (NCT03873805) into MB-105, which will recruit a total of 33 patients with mCRPC that expresses the PSCA protein.

Its primary goals are to investigate the safety of MB-105, and to determine a proper dose for future study. These steps are incorporated into the design of the trial, which is a dose escalation study, meaning that subsequently enrolled patients are given higher treatment doses until the side effects become too severe.

The researchers will also assess treatment efficacy, by measuring the persistence of the CAR T-cells and by evaluating the patients clinically, namely the proportion of those who respond to treatment, their survival outcomes, and changes in cytokines, or proteins that regulate immune responses.

The recent presentation reported the case of a 73-year old man given MB-105 after failing eight previous treatment courses. Four weeks after receiving the CAR T-cell therapy, the man showed a 94% reduction in PSA levels, a near-complete elimination of soft tissue metastasis — assessed via computerized tomography (CT) imaging — and an improvement in bone metastasis seen via magnetic resonance imaging (MRI).

The patient did experience cytokine release syndrome, a potential side effect of CAR T-cell therapy in which cytokines are rapidly released in response to the treatment, causing symptoms that can range from mild to life-threatening.

In this case, clinicians managed his response with Actemra (tocilizumab), an antibody that targets and reduces the activity of the cytokine IL-6. He also had a hemorrhagic cystitis, or an inflammation of the bladder, which required a blood transfusion and was ultimately resolved within 30 days.

Given the improvement in the patient’s mCRPC, Mustang was encouraged by the report, and will be providing further details about MB-105 toward the end of next year.

“We see potential for this PSCA-targeted CAR T in the treatment of prostate cancer, as well as other difficult-to-treat solid tumor cancers,” Litchman said. “We look forward to the continued progression of this trial and anticipate providing further data in the second half of 2021.”

David earned a PhD in Biological Sciences from Columbia University in New York, NY, where he studied how Drosophila ovarian adult stem cells respond to cell signaling pathway manipulations. This work helped to redefine the organizational principles underlying adult stem cell growth models. He is currently a Science Writer, as part of the BioNews Services writing team.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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David earned a PhD in Biological Sciences from Columbia University in New York, NY, where he studied how Drosophila ovarian adult stem cells respond to cell signaling pathway manipulations. This work helped to redefine the organizational principles underlying adult stem cell growth models. He is currently a Science Writer, as part of the BioNews Services writing team.
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