Release date: 2017-10-11
Poseida Therapeutics, a company focused on the development of a new CAR-T therapy, recently announced the results of a preclinical study of P-PSMA-101 for prostate cancer, P-PSMA- at the 24th Annual Prostate Cancer Fund Conference in Washington. 101 exhibits potent anti-tumor activity and a long-lasting response during treatment, resulting in complete elimination of solid tumors in pre-clinical mouse models of prostate cancer that were previously incurable.
Prostate Cancer Foundation Annual Retreat (image source pcf.org)
P-PSMA-101 is a PSMA-specific CAR-T cell candidate for Poseida for the treatment of prostate cancer. It is a gene-editing of the patient's own T cells, which makes it safe and effective to eliminate prostate-specific membrane antigens. An autologous cell therapy of tumor cells (PSMA). (PSMA is overexpressed on the surface of most prostate cancer cells and is further increased in poorly differentiated, metastatic and androgen-independent prostate cancer cells, but extremely low in normal tissues such as kidneys, intestines, etc.).
In this preclinical study, the researchers implanted an invasive and previously incurable human prostate cancer cell line called LNCaP as a solid tumor into an immunodeficient mouse model. Based on this model, P- The efficacy of PSMA-101 was evaluated.
In addition, the researchers compared P-PSMA-101 with another anti-PSMACAR-T therapy in the traditional scFv structure J591 used clinically. The results showed that J591 CAR-T showed marginal efficacy in vitro. However, there is no therapeutic effect on human tumors in animal models.
P-PSMA-101 structure (picture source poseida)
Unlike normal CAR-T cells, Poseida's CAR-T cells do not contain the scFv structure, but consist of a fully humanized Centyrin domain that is engineered based on its proprietary piggyBac non-viral gene delivery system. The streamlined and scalable manufacturing process is completed without the use of viruses, cytokines or magnetic beads, and can continue to produce high concentrations of CAR-T cells required for patient treatment. Compared to the traditional virus-based CAR-T modification system, the productivity of the piggyBac technology platform is 30 times higher.
piggyBac Transposon System (image source poseida)
In addition, a high proportion (> 70%) of memory stem cell-like T cells (Tscm) can be obtained by editing T cells by piggyBac technology, even though the patient's own T cell subtype is very small. (Other CAR-T cells typically contain only 0-20% of such Tscm cells), and Tscm cells may make CAR-T products more effective for patient treatment.
Currently, this theory has been confirmed in preclinical studies. These new CAR-T products developed by Poseida have the common feature of producing a high proportion of memory stem cell-like T cells during treatment, so they produce a strong and effective long-lasting response without secondary treatment.
It was also confirmed in the preclinical study of P-PSMA-101.
Effective anti-tumor activity: After 21 days of treatment with P-PSMA-101, the tumor burden of the mice was reduced to the limit of detection. All untreated control mice died of disease progression.
Sustained response: P-PSMA-101 promoted the production of all T cell subsets for the purpose of continuous treatment of mice, and all treated mice survived until 90 days of study. And when the tumor is completely eliminated, these T cells injected into the mouse contract and again show a major T cell subtype (Tscm).
No T cell depletion was observed: CAR-mediated tonic signaling is a common cause of T cell depletion and also leads to poor durability of CAR-T cells, which are usually caused by traditional scFv CARs. Caused by oligomerization of unstable domains. P-PSMA-101 adopts the PSMA-specific Centyrin domain, so there is no CAR-mediated tonic signal transduction during the treatment, and there is no T cell depletion.
R & D pipeline (picture source poseida)
In this regard, the company's founder and CEO Dr. Eric Ostertag said: "What impressed us most in this trial is that P-PSMA-101 can eliminate the detection limit beyond the invasive cancer cell line (using the previous A tumor that is incurable by treatment.
It is also worth noting that the preclinical findings of this P-PSMA-101 are consistent with the company's preclinical findings for CAR-T therapy for multiple myeloma (P-BCMA-101), which is also clinical. The former model achieved unprecedented efficacy. (Related article: The company's new CAR-T cells for preclinical studies of relapsed and refractory myeloma, effectiveness and persistence highlight the competitiveness of 麦医麦猛 broke the news)
Currently, P-BCMA-101 has conducted Phase I clinical trials for multiple myeloma and is recruiting patients. (Clinical number: NCT03288493), I believe that based on such excellent preclinical research results, P-PSMA-101 can also quickly go to the clinic.
About Poseida Therapeutics
Headquartered in California, PoseidaTherapeutics develops targeted therapeutics in highly unmet medical needs using genome editing technologies such as CRISPR. The company's technology platform has broad applicability and the initial application will focus on gene therapy for multiple myeloma, prostate cancer and beta-thalassemia.
About prostate cancer
With the continuous improvement of life expectancy, the westernization of lifestyle and the advancement of medical testing methods, the incidence of urinary system tumors in China has increased rapidly, especially prostate cancer. According to statistics, the incidence of prostate cancer in China has increased more than tenfold in the past 20 years. It has ranked the top five in male cancer incidence and the highest incidence of urinary system tumors in males. And from the current trend of China's aging and diet development, the incidence of prostate cancer will continue to rise.
Reference source
Http://poseida.com/2017/10/05/
Https://myelomaresearchnews.com/2017/09/13/poseidas-myeloma-specific-car-t-cells-combat-aggressive-cancer-in-mice/
http://?EventItemID=105#.Wbx3doyGPIV
Source: Medical Microphone (micro signal cell-culture-club)
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