Innovative immunotherapies for prostate cancer: understanding the synergies between checkpoint inhibition, CAR T-cell therapy, and next-generation therapeutic modalities

Abstract

Immunotherapy has transformed oncology, yet has only been marginally effective in prostate cancer (PCa), which is a malignancy with a low mutational load and a highly immunosuppressive tumor microenvironment (TME). This critical review is a reflection on the changing position of the innovative immunotherapies in PCa that extends beyond the description stage to synthesize the synergies and constraints of immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, and next-generation modalities such as bispecific T-cell engagers (BiTEs). We assess the mechanistic reasoning of combination therapies, comprising androgen receptor signaling communicators, PARP communicators, and radioligand therapies, which seek to modulate the immunogenicity of the immune-cold PCa TME. Also, we combine new knowledge to novel resistance pathways, including the newly discovered thrombospondin-1-CD47 axis, in the process of T cell exhaustion through calcineurin-NFAT signaling. Although some preclinical data and initial clinical indicators in biomarker-selected subpopulations are promising, the vast majority of Phase III trials of ICIs in unselected populations with metastatic castration-resistant prostate cancer (mCRPC) have failed. This review reveals that the next generation of PCa immunotherapy would not be sequential monotherapies but rather rationally designed multimodal combinations guided by profound molecular and immune profiling to overcome inherent resistance mechanisms.

Keywords

prostate cancer immunotherapy / immune checkpoint inhibitors / CAR T-cell therapy / bispecific antibodies / metastatic castration-resistant prostate cancer (mCRPC) / tumor microenvironment

References

[1] Fay EK, Graff JN. Immunotherapy in Prostate Cancer. Cancers (Basel). 2020; 12: 1752.

[2] Wang I, Song L, Wang BY, Rezazadeh Kalebasty A, Uchio E, Zi X. Prostate cancer immunotherapy: a review of recent advancements with novel treatment methods and efficacy. Am J Clin Exp Urol. 2022; 10: 210-33.

[3] Adusei KM, Nirschl TR, Lee AJ, Shen F, Wang X, Praharaj M, et al. Abstract 170: Targeting of macrophage PI3Kγin prostate cancer using Eganelisib (IPI—549) reprograms immune—suppressive infiltrating macrophages to enhance anti—tumor immune responses and promote immunologically mediated tumor growth. Cancer Res. 2024; 84: 170.

[4] Unal B, Kuzu OF, Jin Y, Hurtado DC, Kuijjer ML, Daugaard M, et al. Abstract 5362: Targeting IRE1α alleviates the immunosuppressive tumor microenvironment in prostate cancer. Cancer Res. 2024; 84: 5362.

[5] Kim TJ, Koo KC. Current Status and Future Perspectives of Checkpoint Inhibitor Immunotherapy for Prostate Cancer: A Comprehensive Review. Int J Mol Sci. 2020; 21: 5484.

[6] Meng L, Yang Y, Mortazavi A, Zhang J. Emerging Immunotherapy Approaches for Treating Prostate Cancer. Int J Mol Sci. 2023; 24: 14347.

[7] Subudhi SK, Vence L, Zhao H, Blando J, Yadav SS, Xiong Q, et al. Neoantigen responses, immune correlates, and favorable outcomes after ipilimumab treatment of patients with prostate cancer. Sci Transl Med. 2020; 12: eaaz3577.

[8] De Velasco MA, Kura Y, Sako N, Ando N, Sakai K, Banno E, et al. Abstract 2877: Profiling of myeloid—derived suppressor cells in Pten—deficient in prostate cancer progression. Cancer Res. 2023; 83: 2877.

[9] Cheng B, Huang H. Expanding horizons in overcoming therapeutic resistance in castration—resistant prostate cancer: targeting the androgen receptor—regulated tumor immune microenvironment. Cancer Biol Med. 2023; 20: 568-74.

[10] Crona DJ, Whang YE. Androgen Receptor—Dependent and —Independent Mechanisms Involved in Prostate Cancer Therapy Resistance. Cancers (Basel). 2017; 9: 67.

[11] Weng C, Assouvie A, Dong L, Beltra J, Budhu S, Mangarin L, et al. Thrombospondin—1—CD47 signaling contributes to the development of T cell exhaustion in cancer. Nat Immunol. 2025; 26: 2296-311.

[12] Farhangnia P, Ghomi SM, Akbarpour M, Delbandi A. Bispecific antibodies targeting CTLA—4: game—changer troopers in cancer immunotherapy. Front Immunol. 2023; 14: 1155778.

[13] Drake CG. Preoperative Immunotherapy for Prostate Cancer: From Bench to Bedside. In: Necchi A, Spiess PE, editors. Neoadjuvant Immunotherapy Treatment of Localized Genitourinary Cancers: Multidisciplinary Management. Cham: Springer International Publishing; 2022. pp. 133—43.

[14] Venturini NJ, Drake CG. Immunotherapy for Prostate Cancer. Cold Spring Harb Perspect Med. 2019; 9: a030627.

[15] Graff JN, Beer TM, Alumkal JJ, Slottke RE, Redmond WL, Thomas GV, et al. A phase II single—arm study of pembrolizumab with enzalutamide in men with metastatic castration—resistant prostate cancer progressing on enzalutamide alone. J Immunother Cancer. 2020; 8: e000642.

[16] Wu Z, Zhang J, Li L, Wang Z, Yang C. Biomarkers in metastatic castration—resistant prostate cancer for efficiency of immune checkpoint inhibitors. Ann Med. 2025; 57: 2426755.

[17] van Wilpe S, Taha T, Rothmann EC, Altshuler E, Park J, Ledet EM, et al. Efficacy of Anti—PD—(L)1 Immunotherapy in Patients with DNA Mismatch Repair—deficient Metastatic Castration—resistant Prostate Cancer. Eur Urol Oncol. 2025; 8: 1020-9.

[18] Velho PI, Antonarakis ES. PD—1/PD—L1 pathway inhibitors in advanced prostate cancer. Expert Rev Clin Pharmacol. 2018; 11: 475-86.

[19] Fizazi K, Drake CG, Beer TM, Kwon ED, Scher HI, Gerritsen WR, et al. CA184—043; Investigators. Final Analysis of the Ipilimumab Versus Placebo Following Radiotherapy Phase III Trial in Postdocetaxel Metastatic Castration—resistant Prostate Cancer Identifies an Excess of Long—term Survivors. Eur Urol. 2020; 78: 822—30.

[20] Beer TM, Kwon ED, Drake CG, Fizazi K, Logothetis C, Gravis G, et al. Randomized, Double—Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy—Naive Castration—Resistant Prostate Cancer. J Clin Oncol. 2017; 35: 40-7.

[21] Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJM, et al. ; CA184—043 Investigators. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration—resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184—043): a multicentre, randomised, double—blind, phase 3 trial. Lancet Oncol. 2014; 15: 700—12.

[22] Rai V. Immune Checkpoint Inhibitor Therapy for Prostate Cancer: Present and Future Prospectives. Biomolecules. 2025; 15: 751.

[23] Venkatachalam S, McFarland TR, Agarwal N, Swami U. Immune Checkpoint Inhibitors in Prostate Cancer. Cancers (Basel). 2021; 13: 2187.

[24] Petrylak DP, Ratta R, Matsubara N, Korbenfeld E, Gafanov R, Mourey L, et al. Pembrolizumab Plus Docetaxel Versus Docetaxel for Previously Treated Metastatic Castration—Resistant Prostate Cancer: The Randomized, Double—Blind, Phase III KEYNOTE—921 Trial. J Clin Oncol. 2025; 43: 1638-49.

[25] Matsubara N, Petrylak D, Ratta R, Korbenfeld E, Gafanov R, Mourey L, et al. Patient—reported Outcomes in KEYNOTE—921: Pembrolizumab with Docetaxel and Prednisone for Patients with Metastatic Castration—resistant Prostate Cancer. Eur Urol Oncol. 2025;[Epub ahead in print].

[26] Lenis AT, Ravichandran V, Brown S, Alam SM, Katims A, Truong H, et al. Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer. Clin Cancer Res. 2024; 30: 3894-903.

[27] Marabelle A, Le DT, Ascierto PA, Giacomo AMD, Jesus—Acosta AD, Delord J, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair—Deficient Cancer: Results From the Phase II KEYNOTE—158 Study. J Clin Oncol. 2020; 38: 1-10.

[28] Wang W, Mei Z, Chen Y, Jiang J, Qu Y, Saifuding K, et al. Immune checkpoint inhibitors for patients with mismatch repair deficient or microsatellite instability—high advanced cancers: a meta—analysis of phase I—III clinical trials. Int J Surg. 2025; 111: 1357—72.

[29] Klümper N, Grünwald V, Hartmann A, Hölzel M, Eckstein M. The Role of Microsatellite Instability/DNA Mismatch Repair Deficiency and Tumor Mutational Burden as Biomarkers in Predicting Response to Immunotherapy in Castration—resistant Prostate Cancer. Eur Urol. 2024; 86: 388-90.

[30] Antonarakis ES, Park SH, Goh JC, Shin SJ, Lee JL, Mehra N, et al. Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker—Unselected Metastatic Castration—Resistant Prostate Cancer: The Randomized, Open—Label, Phase III KEYLYNK—010 Trial. J Clin Oncol. 2023; 41: 3839-50.

[31] Petrylak DP, Ratta R, Matsubara N, Korbenfeld EP, Gafanov R, Mourey L, et al. Pembrolizumab plus docetaxel for patients with metastatic castration—resistant prostate cancer (mCRPC): Randomized, double—blind, phase 3 KEYNOTE—921 study. JCO. 2023; 41: 19.

[32] Powles T, Yuen KC, Gillessen S, Kadel III EE, Rathkopf D, Matsubara N, et al. Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration—resistant prostate cancer: a randomized phase 3 trial. Nat Med. 2022; 28: 144-53.

[33] Fizazi K, Mella PG, Castellano D, Minatta JN, Kalebasty AR, Shaffer D, et al. Nivolumab plus docetaxel in patients with chemotherapy—naïve metastatic castration—resistant prostate cancer: results from the phase II CheckMate 9KD trial. Eur J Cancer. 2022; 160: 61-71.

[34] Graham LS, Montgomery B, Cheng HH, Yu EY, Nelson PS, Pritchard C, et al. Mismatch repair deficiency in metastatic prostate cancer: Response to PD—1 blockade and standard therapies. PLoS One. 2020; 15: e0233260.

[35] Liu J, Fu M, Wang M, Wan D, Wei Y, Wei X. Cancer vaccines as promising immuno—therapeutics: platforms and current progress. J Hematol Oncol. 2022; 15: 28.

[36] Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. ; IMPACT Study Investigators. Sipuleucel—T immunotherapy for castration—resistant prostate cancer. N Engl J Med. 2010; 363: 411-22.

[37] Sheikh NA, Petrylak D, Kantoff PW, Rosa CD, Stewart FP, Kuan L, et al. Sipuleucel—T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration—resistant prostate cancer. Cancer Immunol Immunother. 2013; 62: 137-47.

[38] Zahm CD, Colluru VT, McNeel DG. DNA vaccines for prostate cancer. Pharmacol Ther. 2017; 174: 27-42.

[39] Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. NPJ Vaccines. 2019; 4: 7.

[40] Obara W, Kanehira M, Katagiri T, Kato R, Kato Y, Takata R. Present status and future perspective of peptide—based vaccine therapy for urological cancer. Cancer Sci. 2018; 109: 550-9.

[41] Schuhmacher J, Heidu S, Balchen T, Richardson JR, Schmeltz C, Sonne J, et al. Vaccination against RhoC induces long—lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial. J Immunother Cancer. 2020; 8: e001157.

[42] Cain C. Translating mRNA vaccines. SciBX. 2012; 5: 1273.

[43] Sharma P, Pachynski RK, Narayan V, Flechon A, Gravis G, Galsky MD, et al. Initial results from a phase II study of nivolumab (NIVO) plus ipilimumab (IPI) for the treatment of metastatic castration—resistant prostate cancer (mCRPC; CheckMate 650). JCO. 2019; 37: 142.

[44] van den Eertwegh AJM, Versluis J, van den Berg HP, Santegoets SJAM, van Moorselaar RJA, van der Sluis TM, et al. Combined immunotherapy with granulocyte—macrophage colony—stimulating factor—transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration—resistant prostate cancer: a phase 1 dose—escalation trial. Lancet Oncol. 2012; 13: 509-17.

[45] Boudadi K, Suzman DL, Anagnostou V, Fu W, Luber B, Wang H, et al. Ipilimumab plus nivolumab and DNA—repair defects in AR—V7—expressing metastatic prostate cancer. Oncotarget. 2018; 9: 28561-71.

[46] Wong YNS, Sankey P, Josephs DH, Jones RJ, Crabb SJ, Beare S, et al. Nivolumab and ipilimumab treatment in prostate cancer with an immunogenic signature (NEPTUNES). JCO. 2019; 37: TPS5090.

[47] Fong PC, Retz M, Drakaki A, Massard C, Berry WR, Romano E, et al. Keynote—365 cohort C: Pembrolizumab (pembro) plus enzalutamide (enza) in abiraterone (abi)—pretreated patients (pts) with metastatic castrate resistant prostate cancer (mCRPC). JCO. 2019; 37: 171.

[48] Graff JN, Burgents J, Liang LW, Stenzl A. Phase III study of pembrolizumab (pembro) plus enzalutamide (enza) versus placebo plus enza for metastatic castration—resistant prostate cancer (mCRPC): KEYNOTE—641. JCO. 2020; 38: TPS258.

[49] Galsky MD, Autio KA, Cabanski CR, Wentzel K, Graff JN, Friedlander TW, et al. Clinical and Translational Results from PORTER, a Multicohort Phase I Platform Trial of Combination Immunotherapy in Metastatic Castration—Resistant Prostate Cancer. Clin Cancer Res. 2025; 31: 1463-75.

[50] Huehls AM, Coupet TA, Sentman CL. Bispecific T—cell engagers for cancer immunotherapy. Immunol Cell Biol. 2015; 93: 290-6.

[51] Tian Z, Liu M, Zhang Y, Wang X. Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies. J Hematol Oncol. 2021; 14: 75.

[52] Zhou S, Liu M, Ren F, Meng X, Yu J. The landscape of bispecific T cell engager in cancer treatment. Biomark Res. 2021; 9: 38.

[53] In H, Park M, Lee H, Han KH. Immune Cell Engagers: Advancing Precision Immunotherapy for Cancer Treatment. Antibodies (Basel). 2025; 14: 16.

[54] Dorff T, Horvath LG, Autio K, Bernard—Tessier A, Rettig MB, Machiels J, et al. A Phase I Study of Acapatamab, a Half—life Extended, PSMA—Targeting Bispecific T—cell Engager for Metastatic Castration—Resistant Prostate Cancer. Clin Cancer Res. 2024; 30: 1488-500.

[55] Lim EA, Schweizer MT, Chi KN, Aggarwal R, Agarwal N, Gulley J, et al. Phase 1 Study of Safety and Preliminary Clinical Activity of JNJ—63898081, a PSMA and CD3 Bispecific Antibody, for Metastatic Castration—Resistant Prostate Cancer. Clin Genitourin Cancer. 2023; 21: 366-75.

[56] Dang K, Castello G, Clarke SC, Li Y, Balasubramani A, Boudreau A, et al. Attenuating CD3 affinity in a PSMAxCD3 bispecific antibody enables killing of prostate tumor cells with reduced cytokine release. J Immunother Cancer. 2021; 9: e002488.

[57] Lim EA, Schweizer MT, Chi KN, Aggarwal RR, Agarwal N, Gulley JL, et al. Safety and preliminary clinical activity of JNJ—63898081 (JNJ—081), a PSMA and CD3 bispecific antibody, for the treatment of metastatic castrate—resistant prostate cancer (mCRPC). JCO. 2022; 40: 279.

[58] Heitmann JS, Hackenbruch C, Walz JS, Jung S, Pflügler M, Schlenk RF, et al. Updated results on the bispecific PSMAxCD3 antibody CC—1 for treatment of prostate cancer. JCO. 2024; 42: 2536.

[59] Ayzman A, Pachynski RK, Reimers MA. PSMA—based Therapies and Novel Therapies in Advanced Prostate Cancer: The Now and the Future. Curr Treat Options Oncol. 2025; 26: 375-84.

[60] Kwon W, Joung JY. T—Cell Engager Therapy in Prostate Cancer: Molecular Insights into a New Frontier in Immunotherapy. Cancers (Basel). 2025; 17: 1820.

[61] Scott SA, Marin EM, Maples KT, Joseph NS, Hofmeister CC, Gupta VA, et al. Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab: A single—center experience. Blood Cancer J. 2023; 13: 191.

[62] Kowalski A, Lykon J, Diamond B, Coffey D, Kaddoura M, Maura F, et al. Tocilizumab prophylaxis for patients with multiple myeloma treated with bispecific antibodies. Blood Adv. 2025; 9: 4979-86.

[63] Ludwig H, Terpos E, van de Donk N, Mateos M, Moreau P, Dimopoulos M, et al. Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network. Lancet Oncol. 2023; 24: e255—69.

[64] Piron B, Bastien M, Antier C, Dalla—Torre R, Jamet B, Gastinne T, et al. Immune—related adverse events with bispecific T—cell engager therapy targeting B—cell maturation antigen. Haematologica. 2024; 109: 357-61.

[65] Thompson JA, Schneider BJ, Brahmer J, Zaid MA, Achufusi A, Armand P, et al. NCCN Guidelines^® Insights: Management of Immunotherapy—Related Toxicities, Version 2.2024. J Natl Compr Canc Netw. 2024; 22: 582-92.

[66] Bianchi M, Franchini M, Lekishvili T, Tselempi E, Robinson J, Kaufmann Y, et al. Abstract 3119: Next—generation multi—specific and conditionally activated CD3 Switch—DARPins with CD2 co—stimulation to tackle the current limitations of T cell engagers in solid tumors. Cancer Res. 2025; 85: 3119.

[67] Nolan—Stevaux O, Li C, Liang L, Zhan J, Estrada J, Osgood T, et al. AMG 509 (Xaluritamig), an Anti—STEAP1 XmAb 2+1 T—cell Redirecting Immune Therapy with Avidity—Dependent Activity against Prostate Cancer. Cancer Discov. 2024; 14: 90-103.

[68] Decato BE, Yang Z, Vengco I, Paweletz K, Pati A, Reddy A, et al. Abstract 727: Association of baseline tumor and peripheral biomarker features with efficacy in metastatic castration—resistant prostate cancer patients treated with xaluritamig. Cancer Res. 2025; 85: 727.

[69] Li C, Fort M, Liang L, Moore G, Bernett M, Muchhal U, et al. 718 AMG 509, a STEAP1 x CD3 bispecific XmAb^® 2+1 immune therapy, exhibits avidity—driven binding and preferential killing of high STEAP1—expressing prostate and Ewing sarcoma cancer cells. Regul young investig award abstr. 2020; 8: A430.

[70] Moore GL, Zeng VG, Diaz JE, Bonzon C, Avery KN, Rashid R, et al. A B7—H3—Targeted CD28 Bispecific Antibody Enhances the Activity of Anti—PD—1 and CD3 T—cell Engager Immunotherapies. Mol Cancer Ther. 2025; 24: 331-44.

[71] Newhook L, Bhojane P, Stahl K, Escalante NE, Repenning P, Escanda DP, et al. Abstract 6719: TriTCE Co—Stim: A next generation trispecific T cell engager platform with integrated CD28 costimulation, engineered to improve responses in the treatment of solid tumors. Cancer Res. 2024; 84: 6719.

[72] Kebenko M, Goebeler M, Wolf M, Hasenburg A, Seggewiss—Bernhardt R, Ritter B, et al. A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T—cell engager (BiTE®) antibody construct, in patients with refractory solid tumors. Oncoimmunology. 2018; 7: e1450710.

[73] Einsele H, Borghaei H, Orlowski RZ, Subklewe M, Roboz GJ, Zugmaier G, et al. The BiTE (bispecific T—cell engager) platform: Development and future potential of a targeted immuno—oncology therapy across tumor types. Cancer. 2020; 126: 3192-201.

[74] Mehrabadi AZ, Tat M, Alvanegh AG, Roozbahani F, Ghaleh HEG. Revolutionizing cancer treatment: the power of bi— and tri—specific T—cell engagers in oncolytic virotherapy. Front Immunol. 2024; 15: 1343378.

[75] Cao L, Leclercq—Cohen G, Klein C, Sorrentino A, Bacac M. Mechanistic insights into resistance mechanisms to T cell engagers. Front Immunol. 2025; 16: 1583044.

[76] Le X, Zhang Y, Ma J. Comprehensive analysis of adverse events associated with T—cell engagers using the FAERS database. Expert Opin Drug Saf. 2025; 24: 821—30.

[77] Narayan V, Barber—Rotenberg JS, Jung I, Lacey SF, Rech AJ, Davis MM, et al. PSMA—targeting TGFβ—insensitive armored CAR T cells in metastatic castration—resistant prostate cancer: a phase 1 trial. Nat Med. 2022; 28: 724—34.

[78] Masone MC. Genetically engineered CAR T cells to hack prostate cancer TME. Nat Rev Urol. 2022; 19: 255.

[79] Bhatia V, Koichi S, Jun I, Lee JK. Abstract B010: Targeting Metastatic Prostate Cancer with STEAP1 CAR T Cells and Tumor—Localized Immunomodulation. Cancer Immunol Res. 2025; 13: B010.

[80] Bhatia V, Kamat NV, Pariva TE, Wu L, Tsao A, Sasaki K, et al. Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell and tumor—localized IL—12 immunotherapy. Nat Commun. 2023; 14: 2041.

[81] He C, Zhou Y, Li Z, Farooq MA, Ajmal I, Zhang H, et al. Co—Expression of IL—7 Improves NKG2D—Based CAR T Cell Therapy on Prostate Cancer by Enhancing the Expansion and Inhibiting the Apoptosis and Exhaustion. Cancers (Basel). 2020; 12: 1969.

[82] Zarrabi KK, Narayan V, Mille PJ, Zibelman MR, Miron B, Bashir B, et al. Bispecific PSMA antibodies and CAR—T in metastatic castration—resistant prostate cancer. Ther Adv Urol. 2023; 15: 17562872231182219.

[83] Fajnorova I, Jeanjean P, Azrour IC, Fakharpour A, Liu VJ, Czernin J, et al. Abstract B001: Double targeted therapy PSCA—CAR—T cells and PSMA—radioligand in metastatic castration—resistant prostate cancer. Clin Cancer Res. 2025; 31: B001.

[84] Hirabayashi K, Du H, Xu Y, Shou P, Zhou X, Fucá G, et al. Dual Targeting CAR—T Cells with Optimal Costimulation and Metabolic Fitness enhance Antitumor Activity and Prevent Escape in Solid Tumors. Nat Cancer. 2021; 2: 904—18.

[85] Dorff TB, Blanchard MS, Adkins LN, Luebbert L, Leggett N, Shishido SN, et al. PSCA—CAR T cell therapy in metastatic castration—resistant prostate cancer: a phase 1 trial. Nat Med. 2024; 30: 1636—44.

[86] Slovin SF, Dorff TB, Falchook GS, Wei XX, Gao X, McKay RR, et al. Phase 1 study of P—PSMA—101 CAR—T cells in patients with metastatic castration—resistant prostate cancer (mCRPC). JCO. 2022; 40: 98.

[87] Lickefett B, Chu L, Ortiz—Maldonado V, Warmuth L, Barba P, Doglio M, et al. Lymphodepletion—an essential but undervalued part of the chimeric antigen receptor T—cell therapy cycle. Front Immunol. 2023; 14: 1303935.

[88] Innamarato P, Kodumudi K, Asby S, Schachner B, Hall M, Mackay A, et al. Reactive Myelopoiesis Triggered by Lymphodepleting Chemotherapy Limits the Efficacy of Adoptive T Cell Therapy. Mol Ther. 2020; 28: 2252—70.

[89] Owen K, Ghaly R, Shohdy KS, Thistlethwaite F. Lymphodepleting chemotherapy practices and effect on safety and efficacy outcomes in patients with solid tumours undergoing T cell receptor—engineered T cell (TCR—T) Therapy: a systematic review and meta—analysis. Cancer Immunol Immunother. 2023; 72: 805-14.

[90] Gorchakov AA, Kulemzin SV, Kochneva GV, Taranin AV. Challenges and Prospects of Chimeric Antigen Receptor T—cell Therapy for Metastatic Prostate Cancer. Eur Urol. 2020; 77: 299-308.

[91] Pettitt D, Arshad Z, Smith J, Stanic T, Holländer G, Brindley D. CAR—T Cells: A Systematic Review and Mixed Methods Analysis of the Clinical Trial Landscape. Mol Ther. 2018; 26: 342-53.

[92] The Role of Advanced Practitioners in Optimizing Clinical Management and Support of Patients With Cytokine Release Syndrome From CAR T—Cell Therapy [Internet]. JADPRO; [cited 2024 Nov 6]. Available from: https://www.advancedpractitioner.com/issues/volume—10,—number—8—(novdec—2019)/the—role—of—advanced—practitioners—in—optimizing—clinical—management—and—support—of—patients—with—cytokine—release—syndrome—from—car—t—cell—therapy.aspx

[93] Pennisi M, Jain T, Santomasso BD, Mead E, Wudhikarn K, Silverberg ML, et al. Comparing CAR T—cell toxicity grading systems: application of the ASTCT grading system and implications for management. Blood Adv. 2020; 4: 676-86.

[94] Sun W, Jiang Z, Jiang W, Yang R. Universal chimeric antigen receptor T cell therapy—The future of cell therapy: A review providing clinical evidence. Cancer Treat Res Commun. 2022; 33: 100638.

[95] Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, et al. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J Clin Oncol. 2013; 31: 412-9.

[96] Smith M, De Bono J, Sternberg C, Moulec SL, Oudard S, Giorgi UD, et al. Phase III Study of Cabozantinib in Previously Treated Metastatic Castration—Resistant Prostate Cancer: COMET—1. J Clin Oncol. 2016; 34: 3005—13.

[97] Castellano D, Apolo AB, Porta C, Capdevila J, Viteri S, Rodriguez—Antona C, et al. Cabozantinib combination therapy for the treatment of solid tumors: a systematic review. Ther Adv Med Oncol. 2022; 14: 17588359221108691.

[98] Petrylak DP, Loriot Y, Shaffer DR, Braiteh F, Powderly J, Harshman LC, et al. Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration—Resistant Prostate Cancer: A Phase I Study. Clin Cancer Res. 2021; 27: 3360—9.