In a Dec. 7 Zacks Small-Cap Research note, John Vandermosten explained how RXi Pharmaceuticals Corp.'s (RXII:NASDAQ) self-delivering RNA interference (sd-rxRNA) technology may be used in conjunction with adoptive cell transfer (ACT) cancer therapies to "enhance their effectiveness and durability."
These ACT processes include endogenous T-cell therapy, T-cell receptor-transduced T cells and, currently most researched, tumor infiltrating lymphocyte (TIL) therapy and chimeric antigen receptor T-cell (CAR-T) therapy. The most common disease targets for TIL therapy are melanoma and solid cancers whereas for CAR-T therapy they are leukemia, lymphoma and other blood cancers.
Vandermosten noted that "ACT is especially conducive to combination therapy with interference RNA (RNAi) as it can augment ACT's efficacy, impact expression of immune cell proteins and maintain immune cells in a stem-like state, which enhances their propagation and longevity."
In terms of CAR-T therapies, sd-rxRNA can bolster their effectiveness. For instance, cancer cells can outlast such treatment, and they may evade it by expressing checkpoint receptors that "allow them to hide." Sd-rxRNA can tackle these CAR-T deficiencies by "enhancing the T cells' qualities." One way is by blocking production of checkpoint inhibitors, and with its pipeline, RXi is targeting PD-1 and TIGIT. Another way is by preventing differentiation of the T cells so they divide more slowly and live for a shorter time.
The U.S. Food and Drug Administration in December 2017 approved two different CAR-T therapies, one for youths with acute lymphoblastic leukemia and the other for adults with large B-cell lymphoma.
The Zacks report outlined that another potential role for RXi's technology in CAR-T therapy involves T memory stem cells (TSCMs). These immature cells can enhance the performance of CAR-T therapy through their "characteristics of self-renewal, extended longevity and ability to remember antigens that represent disease threats."
RXi is investigating sd-rxRNA's ability to "maintain greater numbers of T cells in the TSCM-differentiated state," Vandermosten wrote. The biotech is working with partners to advance the preclinical-stage program.
With respect to TIL therapy, potential exists for RXi's sd-rxRNA to augment it as well, the report pointed out. When TILs are being expanded, "interference RNA can be used to modify expression of both intra and extracellular targets including multiple checkpoints and/or targets that influence cell differentiation," Vandermosten described. Minimizing checkpoints, for example, allows the TILs to better identify and kill cancer cells.
RXi Pharmaceuticals continues to form collaborations. Most recently, the company announced a research partnership with the Herlev Hospital in Denmark, which is "developing ACT, TIL-based therapies, genetic engineering of T-cells and other programs which are expected to synergize with RXi's platform," the report relayed.
A second recent partnership is with Gustave Roussy, a European cancer research center, which, Vandermosten wrote, aims to "evaluate sd-rxRNA compounds in a human tumor xenograft model."
RXi is also collaborating with the private firm, BioAxone BioSciences, which is studying sd-rxRNA as a treatment for spinal cord injury.
About RXi's potential for additional programs and partnerships, Vandermosten concluded, "The company's opportunity set is extensive. . .exciting collaborations are possible between RXi's sd-rxRNA and adoptive cell therapy."
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1) Doresa Banning compiled this article for Streetwise Reports LLC and provides services to Streetwise reports as an independent contractor. She or members of her household own securities of the following companies mentioned in the article: None. She or members of her household are paid by the following companies mentioned in this article: None.
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Disclosures from Zacks Small-Cap Research, RXII Pharmaceuticals Inc., Dec. 17, 2017
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