Results from ongoing research by scientists at City of Hope, in Duarte, California, one of the largest cancer research and treatment organizations in the United States, will be presented as late-breaking and clinical trial findings at this year’s annual meeting of the American Association for Cancer Research (AACR), being held April 8-13, 2022 at the Ernest N. Morial Convention Center in New Orleans, Louisiana.

The research showcases the latest discoveries across the spectrum of cancer research, including a pilot program in tobacco use cessation and new developments in cell therapy.

Engineering natural killer cells for a new type of cell therapy
Jianhua YuMichael Caligiuri and colleagues have developed a new cell therapy approach using natural killer cells that, in lab models, induced a greater response against acute myeloid leukemia (AML) and lengthened the survival of mice with AML without damaging healthy blood stem cells.

Based on the initial results, the scientists hope that this treatment could one day provide a viable cell therapy option for patients with AML, who traditionally have not benefited from innovative cell therapy treatments. When these patients experience relapse, it often occurs rapidly, so there is not enough time to prepare patient-derived chimeric antigen receptor (CAR) T cell therapy. The researchers believe that the off-the-shelf cord blood approach they are developing may provide a breakthrough treatment option for a subpopulation of AML patients with the FLT3 gene. [A][1]

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Approximately 30% of all patients diagnosed with AML are FLT3+. These patients have generally a worse prognosis, with higher rates of relapse and lower rates of survival than the overall AML population.[1][2]

As second late-breaking poster will be presented by Ting Lu, Jianhua YuMichael Caligiuri and colleagues have engineered off-the-shelf natural killer cells to make a protein that causes them to be 10 times more potent in killing human lung cancer cells grown in the lab.

When tested in mice transplanted with human non-small cell lung cancer, the innovative cell therapy City of Hope developed worked better than un-engineered natural killer cells and did not appear to affect body weight, liver or kidney function, or blood counts, suggesting a safe and effective approach to test clinically. [B]

Priming brain tumors with an oncolytic virus before CAR T cell therapy 
Christine Brown will present data to support the initiation of a Phase 1 clinical trial combining CAR T cell therapy with a cancer-killing oncolytic viral therapy for the treatment of recurrent glioblastoma. This combination trial builds on interim clinical findings from City of Hope and the University of Alabama at Birmingham (UAB).

A CAR T cell therapy Phase 1 trial being carried out at City of Hope for recurrent glioblastoma suggests that the more immune cells within the tumor, the longer the patient’s survival.

The oncolytic viral clinical Phase 1 trial conducted by UAB used an oncolytic virus engineered for improved gene expression and viral replication to kill specific brain tumor cells. Early findings suggest that the virus could activate immune responses in the brain.

Based on these human clinical trials, the research team treated mice with brain tumors first with the oncolytic virus, then with cell therapy, and showed that together the two treatments did not cause any side effects.

A clinical trial under a Mustang Bio investigational new drug application will soon open to try this combination on two types of brain tumors.[C]

MB-109 combines MB-101 (IL13Rα2-targeted CAR-T cells) CAR T cell therapy with MB-108 (C134 oncolytic virus). The combination is designed to leverage MB-108 to make cold glioblastoma tumors “hot,” and thereby improve the efficacy of MB-101 CAR-T cell therapy.

Clinical data from separate trials, together with results from the in vivo combination studies currently underway, will support the first ever industry-sponsored trial of an oncolytic virus with a CAR-T for the treatment of cancer patients.

Empowering cancer patients to design their own smoking cessation program increases desire to quit
Cary PresantKimlin AshingSteven Rosen and colleagues developed a novel Personal Pathway to Success program where cancer patients were able to choose from 27 individualized tobacco cessation services to help them quit smoking prior to surgery.

The pilot program was offered to 54 patients in a preoperative anesthesia testing clinic, and 23 completed counseling. The availability of the program increased initial patient interest from less than 10% to more than 50% of patients working to quit smoking.

The innovative, personalized intervention program appears to be effective, partially because it reaches cancer patients during pre-surgery visits, when they seem to be more receptive to a “teachable moment” of behavioral changes to prevent disease.[D]

Scheduled presentations
[A] Off-the-shelf cord blood FLT3 CAR-NK cells for immunotherapy of acute myeloid leukemia. Poster Presentation LB102: Monday, April 11, 1:30 to 5 p.m. CT
[B] Tumor-reactive and anti-PD-L1 co-stimulated killer cells (TRACK-NK) for immunotherapy of non-small cell lung cancer. Poster presentation LB211, Wednesday, April 13, 9 a.m. to 12:30 p.m. CT
[C] Oncolytic viral reshaping of the tumor microenvironment to promote CAR T cell therapy for glioblastoma. Poster Presentation CT541, Wednesday, April 13, 9 a.m. to noon CT
[D] Empowering tobacco-using cancer patient initiation of tobacco cessation by a personal pathway to success program during preoperative patient counseling: a feasibility study. Poster Presentation LB553, Friday, April 8, noon to 1 p.m. CT

[1] Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017;141(10):1342-1393.
[2] Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Hematology Am Soc Hematol Educ Program. 2013;2013:220-226.

Featured image: City of Hope. Courtesy 2016 City of Hope, Duarte, CA.

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