scholarly journals Doxorubicin-loaded Black Phosphorus Multifunctional Nanodelivery System Combined With Photothermal Therapy Promotes Immunogenic Death of Prostate Cancer PC-3 cells.

2021 ◽  
Author(s):  
Linfeng Li ◽  
Li Gao ◽  
Haoyang Xu
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Photothermal Therapy ◽  
Prostate Cancer Cell ◽  
The Body ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Insidious Onset ◽  
High Immunogenicity ◽  
Dc Maturation

Abstract Prostate cancer is the second most harmful malignant tumor in men because of its insidious onset, easy metastasis, and easy development into castration-resistant prostate cancer even after treatment. Due to its high immunogenicity and a small number of specific infiltrating T cells with tumor-associated antigens in the tissue, it is difficult to obtain a good therapeutic effect with immune checkpoint blocking therapy alone. Therefore, in the current study, we developed a platform carrying Doxorubicin (DOX)-loaded black phosphate nanometer combined with photothermal therapy (PTT) and found this drug combination stimulated the immungentic cell death (ICD) process in PC-3 cells and DC maturation, allowing the DCs to present the related antigens and stimulate the body to produce more of CD8+ T cells, leading to a stronger immune response.More importantly, the introduction of Zn2+ and Aptamer (Apt) improved the prostate cancer cell killing ability of the nanosystem.

A phase I clinical trial of PSMA-directed/TGFβ-insensitive CAR-T cells in metastatic castration-resistant prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 125-125
Author(s):  
Vivek Narayan ◽  
Julie Barber-Rotenberg ◽  
Joseph Fraietta ◽  
Wei-Ting Hwang ◽  
Simon F. Lacey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
T Cells ◽  
Cell Expansion ◽  
Castration Resistant Prostate Cancer ◽  
Car T Cells ◽  
Castration Resistant ◽  
Car T ◽  
Tumor Biopsies ◽  
Dose Dependent

125 Background: Prostate specific membrane antigen (PSMA) is a highly expressed tumor-associated antigen potentially amenable to chimeric antigen receptor-modified T (CAR-T) cell therapy for castration-resistant prostate cancer (CRPC). However, a primary challenge to the success of CAR-T therapy in CRPC is the immunosuppressive microenvironment, characterized by high levels of TGFβ. The immunosuppressive functions of TGFβ can be inhibited in T cells using a dominant negative TGFβ receptor (TGFβRdn), thereby enhancing antitumor immunity. Methods: We conducted a first-in-human phase 1 clinical trial to evaluate the feasibility, safety and preliminary efficacy of PSMA-directed/TGFβ-insensitive CAR-T cells (CART-PSMA-TGFβRdn) in patients with metastatic CRPC (NCT03089203). In a 3+3 dose-escalation design, patients received a single dose of 1-3 x 107/m2 (Cohort 1) or 1-3 x 108/m2 (Cohort 2) CART-PSMA-TGFβRdn cells without lymphodepleting (LD) chemotherapy. In Cohort 3, one patient received 1-3 x 108/m2 CART-PSMA-TGFβRdn cells following a LD chemotherapy regimen of cyclophosphamide and fludarabine (Cy/Flu). In Cohort -3, three patients received 1-3 x 107/m2 CART-PSMA-TGFβRdn cells following Cy/Flu. Patients underwent metastatic tumor biopsies at baseline and on day 10 following treatment. Quantitative PCR of CART-PSMA-TGFβRdn DNA was performed at serial timepoints to evaluate for CAR-T expansion and persistence in peripheral blood and trafficking to target tissues. Multiplex cytokine analysis assessed CART-PSMA-TGFβRdn bioactivity. Results: Ten patients received CART-PSMA-TGFβRdn therapy across dose-level cohorts. All CART-PSMA-TGFβRdn infusion products met target transduction efficiency. Evaluation of CAR-T cellular kinetics demonstrated dose-dependent peripheral blood T cell expansion, as well as tumor tissue trafficking in post-treatment tumor biopsies. At Cohort 2 and above, 5 of 7 treated patients developed grade ≥2 cytokine release syndrome (CRS). Marked increases in inflammatory cytokines (IL-6, IL-15, IL-2, IFNγ) correlated with high-grade CRS events. One grade 5 adverse event (sepsis) occurred in Cohort 3. PSA decline was observed in 6 of 10 patients (median decline -33.2%, range -11.6% to -98.3%), and PSA30 response occurred in 4 of 10 patients (including one patient achieving PSA < 0.1 ng/mL). Conclusions: Adoptive cellular therapy with CART-PSMA-TGFβRdn is safe and feasible in patients with metastatic CRPC. A dose-dependent and lymphodepletion chemotherapy-dependent relationship was observed with CART-PSMA-TGFβRdn cell expansion, cytokine expression, CRS, and anti-tumor effect. Correlative cell trafficking and paired tumor Nanostring analyses will be presented. Future clinical investigations seek to enhance anti-tumor efficacy, while optimizing the therapeutic window. Clinical trial information: NCT03089203.

scholarly journals Apalutamide: a better option for the treatment of non-metastatic castration resistant prostatic carcinoma

2018 ◽  
Vol 7 (9) ◽  
pp. 1853 ◽  
Author(s):  
Raushan Kumar Ranjan ◽  
Akash Chandra
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
The Body ◽  
Blood Levels ◽  
Gnrh Analogue ◽  
Castration Resistant Prostate Cancer ◽  
Reductase Inhibitors ◽  
Castration Resistant ◽  
Cancer Of The Prostate

Prostate cancer is cancer of the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, some grow relatively quickly. The cancer cells may spread from the prostate to other area of the body, particularly the bones and lymph nodes. Factors that increase the risk of prostate cancer include older age, a family history of the disease, and race. About 99% of cases occur in males over the age of 50. Clinical features include hematuria, dysuria (painful urination),nocturia(urination at night). Lower blood levels of vitami D may increase the risk of developing prostate cancer. Infection with the sexually transmitted diseases, chlamydia, gonorrhea, syphilis and prostatitis seem to increase risk of prostate cancer. Diagnosis can be confirmed by digital rectal examination (DRE) with prostate-specific antigen (PSA) blood test, cystoscopy, transrectal ultrasonography and biopsy (The removal of small pieces of the prostate for microscopic examination). Medicines like 5-alpha-reductase inhibitors (finasteride and dutasteride) reduce the overall risk of prostate cancer. Apalutamide, sold under the brand name Erleada, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is specifically indicated for use in conjunction with castration in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC). It is taken by mouth. Apalutamide was first described in 2007 and was approved for the treatment of prostate cancer in February 2018. Apalutamide is used in conjunction with castration, either via bilateral orchiectomy or gonadotropin-releasing hormone analogue (GnRH analogue) therapy, as a method of androgen deprivation therapy in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC).

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