[Madrid, Spain = E-Daily Reporter Kim Jinsoo ] It has been confirmed that “VCB-1201,” a multiple myeloma cell therapy currently under development by Vaxcell-Bio Therapeutics(323990), achieved a 100% survival rate over 120 days in preclinical animal trials. The therapy demonstrated superior antitumor activity and survival outcomes compared to existing chimeric antigen receptor T-cell (CAR-T) therapies. Vaxcell-Bio Therapeutics is also conducting experiments to directly compare the efficacy of its therapy with Johnson & Johnson’s (J&J) multiple myeloma CAR-T therapy, “Kavicti,” to enhance its competitiveness.

Baek Min-woo, Deputy Director of the R&D Center at Vaxcell-Bio Therapeutics, met with Edaily at the European Society for Medical Oncology (ESMO) conference held in Madrid, Spain, and stated, “In a mouse model of multiple myeloma, all subjects administered CAR-MIL survived throughout the approximately 120-day observation period, maintaining a 100% survival rate. In contrast, some mice in the group treated with the existing CAR-T therapy died, demonstrating a clear difference.”

At this year’s ESMO, Vaxcell-Bio Therapeutics presented preclinical trial data evaluating the antitumor activity and in vivo persistence of VCB-1201, a CAR-MIL therapy based on bone marrow-infiltrating lymphocytes (MIL) currently under development. Vaxcell-Bio Therapeutics directly compared conventional peripheral blood-derived CAR-T with CAR-MIL in in vitro experiments using patient-derived multiple myeloma cells and in animal studies.

In the animal studies, multiple myeloma cells were transplanted into mice, and CAR-T or CAR-MIL was administered approximately one week later. Subsequent observations of tumor growth and survival duration confirmed superior tumor suppression and long-term survival in the CAR-MIL treatment group.

Center Director Baek explained, “While the extent of tumor reduction in animal studies is important, the most notable factor is how long the animals survive,” adding, “In mice treated with conventional CAR-T, some died over time, but the CAR-MIL group maintained long-term survival.”

Based on these research findings, Vaxcell-Bio Therapeutics has also initiated a direct comparison with a globally commercialized therapy. The comparator is “Kavikti,” a BCMA-targeted CAR-T therapy jointly developed by Johnson & Johnson (J&J) and Legend Biotech. Kavikti received approval from the U.S. Food and Drug Administration (FDA) in 2022 and is currently used to treat relapsed or refractory multiple myeloma.

Center Director Baek stated, “The data presented at this year’s ESMO conference compares peripheral blood-derived CAR-T cells and bone marrow-derived CAR-MIL cells that both incorporate the same CAR gene,” adding, “We are conducting separate comparative trials with the FDA-approved Cabicti.”

The key differentiator of VCB-1201 lies in the origin of the immune cells used to manufacture the therapy. Conventional CAR-T therapies extract T cells from a patient’s peripheral blood and introduce CARs that recognize cancer cells. In contrast, CAR-MIL introduces CARs into MIL cells extracted from the patient’s bone marrow. Both therapies target the B-cell maturation antigen (BCMA), which is highly expressed on multiple myeloma cells.

He explained, “If conventional CAR-T is a method of equipping cells that have never fought cancer cells with weapons, CAR-MIL is a concept of equipping cells that already possess the ability to fight cancer cells with additional weapons,” adding, “Bone marrow-derived T cells possess their own cytotoxic activity against multiple myeloma cells even before the CAR is introduced.”

This means that CAR-MIL can simultaneously leverage both the CAR-mediated targeting of BCMA and the existing antitumor function mediated by the T-cell receptor (TCR). In actual studies, blocking the TCR-mediated cytotoxic function of CAR-MIL reduced its ability to kill cancer cells. In contrast, peripheral blood-derived CAR-T cells showed no change in efficacy when blocked in the same manner.

Deputy Director Baek stated, “The fact that the anticancer effect decreased significantly when CAR-MIL’s unique function was blocked is clear evidence that this function contributes to the therapeutic effect.”

Differences were also observed in their ability to persist in the body over the long term. Vaxcell-Bio Therapeutics extracted and compared CAR-T and CAR-MIL cells that had infiltrated tumors and found that CAR-MIL exhibited higher expression levels of CD69—a marker of T-cell activation—and CXCR4, which is involved in tumor migration. Markers associated with attacking cancer cells, such as interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), also increased.

Manufacturing Process

Established

in 10 Days… Planning to File IND Application in June Next Year

Vaxcell-Bio Therapeutics has also established a manufacturing

process

to advance VCB-1201 into clinical trials. Since CAR-MIL requires T cells to be sourced from bone marrow rather than peripheral blood, the initial cell count is relatively low. Therefore, proliferation technology to secure sufficient therapeutic cells is key.

Vaxcell-Bio Therapeutics has standardized the time required from bone marrow cell collection to the production of the final CAR-MIL to 10 days. Since the limited initial cell count can be expanded by approximately 100 to 120 times to yield a final cell count of about 700 million to 1 billion cells, high therapeutic efficacy is anticipated.

Vaxcell-Bio Therapeutics is also conducting trials using cells produced in GMP facilities and plans to begin GLP toxicity, efficacy, and in vivo distribution studies using GMP-manufactured cells starting this November.

Center Director Baek stated, “We are concurrently conducting thorough validation for the clinical trial application, including cross-reactivity with normal human tissue, the potential for off-target binding to approximately 3,000 types of cell membrane proteins, and the safety of the viruses used for gene delivery,” adding, “We aim to submit an IND application around June 2027 after synthesizing the relevant test results and safety data.”