Umoja's in vivo CAR-T therapy shows positive first signs in primates

Umoja Biopharma’s VivoVec platform has generated in vivo chimeric antigen receptor T cells, or CAR-T cells, in nonhuman primates, according to new data presented by the company Sept. 1 during the annual CAR-TCR Summit in Boston. The CAR-Ts also appeared to have activity against target cells and continued proliferating for more than a month in one of the animals.

"Our hope is that the replication of these data in our early clinical trials will lead to a new class of in vivo CAR-T cell therapeutics that expand the breadth of reach of CAR-T cell therapies by reducing costs and logistical complexity of delivery and by offering an immediate, off-the-shelf, product that generates autologous, patient-specific CAR-T cells," Andy Scharenberg, M.D., Umoja's co-founder and CEO, told Fierce Biotech Research via email.

Umoja’s technology programs a patient's T cells against their cancer in vivo—that is, without ever having to remove the T cells from their body, as currently approved therapies require, or transferring them from donors as occurs with next-generation allogeneic therapies like Allogene's. Instead, Umoja uses lipid nanoparticles it's dubbed VivoVec particles to activate, integrate and express the CAR in a patient’s own T cells.

This replaces the expensive, time-consuming process of extracting and transducing the cells with CARs using viral vectors before re-implanting them back into the patient, steps that can be marred by vector shortages and the possibility of manufacturing failure or low yields. The platform also negates the need for chemotherapy to clear out a patient’s blood cells.

Back in May at the American Society of Gene & Cell Therapy’s annual conference, Umoja reported preclinical data on VivoVec in mice. In the new studies, the researchers injected four male and female pigtail macaque monkeys in the groin-area lymph nodes with a single, clinically relevant dose of the VivoVec particles designed to generate anti-CD20 CARs, the type used to target B-cell lymphoma. The team then monitored the animals for CAR-T cell activation and expansion as well as toxicity. None of the monkeys received chemotherapy beforehand.

In three of the primates, CD20 CAR-T cells peaked at about 40% to 60% of total circulating T cells at their peak. The same three monkeys also had persistent B-cell aplasia, a sign that the CAR-Ts were working.

The numbers for most of the animals exceeded the benchmark for ex vivo CAR-T therapies in a similar primate model, Scharenberg told Fierce. In a 2018 study on rhesus macaque monkeys that underwent chemotherapy followed by CAR-T infusion, the engineered cells proliferated to a peak of 272 to 4,450 CAR-T cells per microliter; their B-cell aplasia lasted between 35 and 42 days. 

In Umoja's latest study, the CAR-T cells in two of the monkeys peaked at between 5,000 and 10,000 cells per microliter and their B-cell aplasia lasted beyond 42 days. In another, the researchers detected a large secondary CAR-T cell expansion around Day 49 or 50, "suggesting that VivoVec may capture aspects of memory T cell biology that are difficult or impossible to capture with ex vivo CAR-T cell manufacturing processes," Scharenberg wrote.

While the therapy was largely well tolerated, there were a few side effects in two of the animals—though none out of the ordinary for CAR-T therapy, and less serious than what was seen in the 2018 study on an ex vivo treatment. The most serious was a mild cytokine release syndrome and neurotoxicity event that culminated in a single seizure, to which the monkey responded to single doses of the appropriate medications.

The primate experiments are ongoing; more data from them will be presented at medical conferences in the fall, Umoja said in the release. The company currently has a piece of its technology in clinical trials at Seattle Children’s Hospital and plans to submit a request to the FDA in the first half of 2024 to take its first VivoVec-based therapy into human studies.

Editor's note: This story has been updated to clarify the technology in clinical trials at Seattle Children's Hospital and the timeline for submitting a request for its first VivoVec-based therapy.