Trial Underway Testing Engineered Cancer-Killing Viruses

Brain tumor (National Science Foundation)

18 July 2023. A clinical trial, testing stem cells for neurons fortified with tumor-killing viruses, administered its first doses to a patient with glioma, an aggressive type of brain cancer. The study is conducted at City of Hope Medical Center, a cancer research and treatment hospital in Duarte, California, evaluating a therapy developed by Calidi Biotherapeutics Inc. in San Diego.

Calidi Biotherapeutics is a biotechnology enterprise designing cancer treatments with engineered mesenchymal or adult stem cells derived from existing tissue, such as from bone, fat, or umbilical cords. The company’s lead product, code-named CLD-101, is made from neural stem cells, precursors to neuron cells in the brain or spinal cord, altered to express a synthetic adenovirus that generates an oncolytic or cancer-killing immune response. Calidi Bio is testing CLD-101 as a treatment for gliomas, a family of cancers in glial cells in the brain that includes glioblastoma, an aggressive type of brain cancer. The therapy is injected by surgeons in the brain cavity walls after surgical removal of the tumor.

The company earlier assessed CLD-101 for safety and to determine a maximum safe single dose among 12 glioma patients, all but one with glioblastoma. The findings, published in the journal The Lancet Oncology in June 2021, indicate treatments are safe with no inherent dose-limiting toxicities, and the authors recommending proceeding with further clinical studies. The authors also report patients experienced progression-free survival of more than nine months and overall survival of more than 18 months. The trial did not have a placebo or comparison group.

The new clinical trial is evaluating the safety and tolerability of CLD-101 in multiple doses among patients. The study team is enrolling 36 participants with recurring and metastatic glioblastoma and other gliomas at City of Hope Medical Center and eventually other sites. Surgeons are giving up to four doses of CLD-101 to patients following removal of their brain tumors, with participants tracked first for 30 days, then another two years. Like the first trial, this study has no placebo or comparison group.

Tumors that survive radiation and chemotherapy

The researchers are looking primarily for any adverse effects of the treatments in the 30 days following surgery, as well as early signs of clinical effects including immune responses from the oncolytic viruses delivered by the neural stem cells or NSCs, and migration of those viral particles inside and outside the brain. In addition, the team is following-up over two years with patients to assess progression-free and overall survival, immune cell populations in the microenvironment supporting tumor growth, and changes in tumor growth.

“Recurrent glioblastoma is notoriously challenging to treat,” says Jana Portnow, co-director of City of Hope’s brain tumor program and principal investigator of the trial in a Calidi Biotherapeutics statement. “These are resistant tumor cells that have survived radiation and chemotherapy and spread to other regions of the brain.” Portnow adds, “CLD-101 is designed to protect and better distribute the anti-cancer virus to sites of tumors distant from the main tumor mass.”

Karen Aboody, scientific leader of the neuro-oncology disease team at City of Hope and an adviser to Calidi Bio notes, “In contrast to the administration of free oncolytic virus, which is rapidly inactivated by the patients’ immune cells, our tumor-targeting NSCs act as a kind of ‘Trojan horse,’ shielding and protecting the anti-cancer virus en route to tumor sites.”

The clinical trial is funded by a $12 million grant from California Institute for Regenerative Medicine. National Cancer Institute, part of National Institutes of Health, is collaborating on the study. City of Hope is part of National Cancer Institute’s Glioblastoma Therapeutics Network, a consortium of academic brain tumor centers.

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