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Randi Hernandez was science editor at BioPharm International from September 2014 to May 2017.
The pharma company revealed in a fourth quarter call that it will improve its cell-culture capabilities by focusing on the use of naïve, highly proliferative cells to manufacture its CAR-T drug candidate.
Kite Pharma noted in a fourth-quarter earnings call that the company has been studying different cell types within its final product to determine which phenotype of T cell is the best producer of quality effector cells. David Chang, chief medical officer and executive vice-president of research and development at Kite Pharma, said that in the past two to three years, the company has been trying to "skew the cell population to more naïve cells, because all the data indicate naïve cells are the ones that expand better and [are] more potent in terms of antitumor activity."
Cell-culturing methods have been found to influence cell phenotype, and according to previous studies conducted by Barrett et al., "cells with a younger phenotype or higher proliferative capacity perform better in preclinical models." Cells with younger phenotypes are often called naïve cells or cells with stem memory phenotypes. Barrett et al. said that many early studies on chimeric antigen receptor T cells (CAR-T) were not successful because there were issues with the proliferation and persistence of cells following adoptive transfer.
Chang attributed the success of Kite's investigational product candidate, KTE-C19, to the fact that the company has improved its cell-culture methodologies. "So one thing that we haven’t really talked about much is just the process of shortening the cell expansion duration," said Chang, who added that a shorter cell-expansion period could drastically improve cell proliferation. "Our manufacturing takes about six to eight days, and the shorter the duration of cell expansion allows you to keep the cells in a much more naïve state ... that alone I believe has led our KTE-C19 product to be more potent."
The company is evaluating other methods to improve its cell-culture methodologies, noted Chang. "There are other ways to continue to keep the cells naïve and that includes using different cytokines during the cell manufacturing process or using inhibitors of certain pathways to keep the cells from differentiating." He added, "as we move forward with the next-generation products-T-cell receptor products-we’ll talk a lot more about how we’re refining the manufacturing itself to keep the cells more potent. And therefore, hopefully, they will work much better clinically."
Source: Seeking Alpha