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ASCO 2021: Converting Peripheral Blood Mononuclear Cells Into Autologous Cellular Therapy for CLL

By: Julia Fiederlein
Posted: Thursday, July 1, 2021

According to James A. Lederer, MS, PhD, of Harvard Medical School, Boston, and colleagues, engineered immunostimulatory cells can convert peripheral blood mononuclear cells from patients with chronic lymphocytic leukemia (CLL) into antitumor effector cells. Their findings, which were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 7517), support the feasibility of converting peripheral blood mononuclear cells into an autologous cellular therapy.

“We demonstrate for the first time that peripheral blood mononuclear cells from patients with CLL can be converted into [antitumor effector cells] despite low numbers of normal immune cells at baseline and the known immunologic impairment present in patients with CLL,” the investigators remarked. “[Antitumor effector cells] derived from patients with CLL acquire potent tumor killing activity that is indistinguishable from [antitumor effector cells] prepared from normal healthy volunteers.”

The results of mass cytometry staining of peripheral blood mononuclear cells from patients with CLL showed approximately 95% leukemia cells and few T cells, natural killer cells, B cells, and monocytes. Mass cytometry staining of antitumor effector cells from all 10 patients with CLL revealed expansion of natural killer cells (17%), CD8 T cells (11%), and CD4 T cells (7.5%) that seemed to be similar in phenotype to those from normal healthy volunteers; high expression of granzymes and perforin was detected, which is indicative of tumor cell killing activity. In the original CLL peripheral blood mononuclear cell samples, the percentage of cancer cells was reduced to 0.8%. A population of non-T/non-B cells (60%) was identified in the antitumor effector cell samples from all patients with CLL; further characterization is required. The rates of tumor cell killing by antitumor effector cells prepared from patients with CLL (77.8% at 2:1) and normal healthy volunteers (81.5% at 2:1) were found to be nearly identical at all effector-to-target ratios. 

Disclosure: Dr. Lederer reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.



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