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Therapeutic Options for Prostate Cancer: A Contemporary Update
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sakthivel Muniyan, Jawed A. Siddiqui, Surinder K. Batra
Sipuleucel-T (Provenge) is the only FDA approved biological therapy for advanced PCa. Sipuleucel-T is the first T cell-associated tumor immunotherapeutic vaccine for mCRPCa. Provenge is composed of the PAcP antigen (full-length PA2024 linked to an adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF)), autologous peripheral blood mononuclear cells (PBMCs) and the activated antigen presenting cells (APCs). Sipuleucel-T works based on the principle of activating one’s immune system to kill the foreign (tumor) cells. Sipuleucel-T has been developed with the combination of recombinant tumor antigens (PAcP) infused into the patients’ blood with their own activated APCs to induce an immune response against the tumor-associated antigen (TAA).
Prostate Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Malcolm Mason, Howard Kynaston
Currently, in addition to abiraterone and enzalutamide, several other systemic therapies have also been shown in Phase III trials to prolong survival in metastatic CRPC, albeit by a modest few months. Not all of these agents are universally available as yet. Cabazitaxel is a novel taxane, which showed a survival benefit compared with mitoxantrone in patients progressing during or soon after docetaxel therapy. Although the duration of survival benefit has been insufficient for its approval in the National Health Service, it was striking to see such activity in such a poor-risk group of patients.67 Sipuleucel-T is a complex immunotherapy delivered by treating autologous dendritic cells ex-vivo with a combination of prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor, following which they are re-infused. Published evidence from the main Phase II trial indicates that this, too, prolongs survival in metastatic CRPC. The logistics of delivering this treatment have precluded its widespread use outside the United States, but this is likely to change in the next few years. Another recent development has been the report of a Phase III, placebo-controlled trial of radium-223 (an alpha emitter) in patients with symptomatic bone metastases, which has demonstrated a significant overall survival benefit.68
Basic Science and Molecular Oncology
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Paul Cleaveland, Vijay Sangar, Noel Clarke
Sipuleucel-T is an autologous cellular immunological agent. The mechanism of action is unknown; however, it is thought to work through antigen-presenting cells to stimulate a T-cell immune response targeted against prostatic acid phosphatase (an antigen highly expressed in prostate cancer cells).
Immunotherapy as a partner for HER2-directed therapies
Published in Expert Review of Anticancer Therapy, 2021
Guy T Clifton, and George E Peoples
Immunotherapy, primarily in the form of immune checkpoint inhibitors, has provided substantial benefit for a minority of cancer patients. While targeting CTLA-4, PD-1/PD-L1 and multiple novel immune checkpoints are being heavily studied in hopes of extending the reach of this class of therapy, the margin of clinical benefit with newer approved indications has decreased over time [72]. For cancer vaccines, the one therapy approved by the FDA 10 years ago, sipuleucel-T, is used in a small percentage of eligible hormone-refractory prostate cancer patients [73]. While developing immune therapies to modulate new targets is important, combining existing immunotherapies with conventional treatments may allow both to work more effectively and is quicker and less costly to study than novel, unique drugs. Certainly, there is increased recognition that concurrent cytotoxic chemotherapy can enhance immunotherapy [74]. Indeed, atezolizumab is conditionally approved for metastatic triple-negative breast cancer only when it is given in combination with nab-paclitaxel [75].
Pharmacotherapeutic strategies for castrate-resistant prostate cancer
Published in Expert Opinion on Pharmacotherapy, 2020
Mohamad Moussa, Athanasios Papatsoris, Mohamed Abou Chakra, Despoina Sryropoulou, Athanasios Dellis
Sipuleucel-T has been used for the treatment of asymptomatic or minimally symptomatic mCRPC patients. Patients most suited to sipuleucel-T treatment are those with lower disease burden and lower PSA baseline values. There is an absence of markers to identify eligible patients and to assess treatment response for sipuleucel-T. The asymptomatic or minimally symptomatic disease may be defined by the absence of opioids prescribed. The infusion related side effects associated with sipuleucel-T are commonly chills, fever, fatigue, nausea, and headache, and they can be prevented if patients were pretreated with acetaminophen. The mechanism of action of sipuleucel-T does not overlap with any other approved treatment. Therefore, cross-resistance between sipuleucel-T and other available agents is not a concern.
Advancing therapies in metastatic castration-resistant prostate cancer
Published in Expert Opinion on Pharmacotherapy, 2018
Giulia Baciarello, Marco Gizzi, Karim Fizazi
Evidence suggests that the immune system may play an important role in PCa pathogenesis and progression [38]. Furthermore, PCa express several specific tumor-associated antigens like prostate-specific antigen (PSA), prostatic acid phosphatase (PAP) and prostate-specific membrane antigen (PSMA), which can be used as targets for immunotherapy. In the last two decades, immunotherapy has been an active field of investigation in mCRPC. Sipuleucel-T is a therapeutic vaccine that stimulates T cell immune responses against tumor. It is the only immunotherapy that showed a statistically significant improvement in overall survival in PCa and it is approved in the United States for men with asymptomatic or minimally symptomatic disease [11]. On the other hand, the CTLA-4 inhibitor ipilimumab initially failed to show improved survival in men pretreated by docetaxel although survival was better in the ipilimumab arm in a long-term, post-hoc analysis (p = 0.03), due to excess in long-term survivors [39,40]. An analysis with even longer-term follow-up is soon awaited.