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Prostate Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Malcolm Mason, Howard Kynaston
An older tumor marker—prostatic acid phosphatase—is occasionally helpful, for example in immunochemistry. Two other potential tissue markers, used in research, are prostate membrane-specific antigen (PSMA) and prostate stem-cell antigen (PSCA). At the moment, they are not useful in routine clinical practice. More recently, the PC3a test, which directly measures genes identified in prostate cancer cells from a urine specimen, has been investigated to determine whether its use in combination with PSA might improve diagnostic sensitivity and specificity. It has not yet found widespread adoption, however.
The Treatment of Advanced Prostatic Cancer with Drugs and Hormones
Published in Nicholas Bruchovsky, James H. Goldie, Drug and Hormone Resistance in Neoplasia, 2019
One final hope is the development of new weapons with a higher and broader cell kill, or less toxicity. New drugs with different mechanisms of action are becoming less frequent, but analogues of agents such as adriamycin and cisplatin may have some advantage. A more selective approach is to develop agents which exploit cellular differences of prostatic tissue, which does not comprise a vital organ. Drugs activated by prostatic acid phosphatase can be synthesized.282 Analogues of 5α-dihydrotestosterone can irreversibly inhibit 5α-reductase.283 Alkylated steroids have been discussed earlier. All these classes are likely to require a fairly well-differentiated cellular mechanism to home onto, and therefore their utility would be in early rather than late systemic treatment.
Localization of Steroid Binding in Prostatic Carcinoma by Histochemistry: Therapeutic Implications *
Published in P. Pertschuk Louis, Lee Sin Hang, Localization of Putative Steroid Receptors, 2018
Louis P. Pertschuk, Richard J. Macchia, Karen B. Eisenberg
In order to determine if there was any relationship between the presence of prostatic acid phosphatase (PAP) and androgen binding, we processed 81 specimens of prostatic carcinoma in parallel for both of these tumor markers. For PAP detection, an IF procedure was used employing a 1:200 dilution of a potent, polyclonal antiserum, made in goat and generously donated by Dr. Chu Ming of the Roswell Park Memorial Institute. Ethanol-fixed frozen sections were reacted wtih the PAP antiserum and then labeled with fluoresceinated rabbit-anti-goat immunoglobulin.
The safety and efficacy of CAR-T cells in the treatment of prostate cancer: review
Published in Biomarkers, 2022
Othman Mohammad Saleh, Khaled Anwer Albakri, Yasmeen Jamal Alabdallat, Majd Hamdi Dajani, Walaa Bayoumie El Gazzar
The initial and most important step to achieve the utmost effective CAR-T cell therapy is to identify prostate TAA (Tumour-Associated Antigens). Targeting a tumour-restricted antigen should be considered to avoid immune reactions against healthy tissues (Hinrichs and Restifo 2013, Mirzaei et al.2017). Prostate tumours contain several tumour-specific antigens like prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA), and although these have limited antigenicity, their high specificity makes these antigens prime candidates for immunotherapies (Correale et al.1997, Knight et al.2009, Olson et al.2010). Therefore, many clinical trials have recently concentrated on the use of TAAs as an activation method to cause an immunological reaction in prostate cancer patients and showed promising findings stated that this strategy is safe and feasible (Kiessling et al.2012, Westdorp et al.2014).
Targeting the spectrum of immune checkpoints in prostate cancer
Published in Expert Review of Clinical Pharmacology, 2021
Laura A. Sena, Samuel R. Denmeade, Emmanuel S. Antonarakis
Perhaps a more promising approach is to boost immune responses to weak but ubiquitously expressed endogenous tumor antigens, such as prostatic acid phosphatase (PAP), the androgen receptor (AR) or prostate-specific antigen (PSA), through vaccines (Table 1). Sipuleucel-T is an autologous cellular therapy in which patients’ antigen-presenting cells (APCs) are extracted, loaded and stimulated with PAP ex vivo, and re-infused. This leads to antigen-specific T cell activation [79] and immune-cell recruitment into tumor [80] and confers a median 4.1 month increase in OS [81]. Small trials of sipuleucel-T in combination with ipilimumab [82] or pembrolizumab [83] reported encouraging results that may indicate synergy. A larger trial of ipilimumab in combination with sipuleucel-T is ongoing (NCT01804465).
Heterologous vaccination targeting prostatic acid phosphatase (PAP) using DNA and Listeria vaccines elicits superior anti-tumor immunity dependent on CD4+ T cells elicited by DNA priming
Published in OncoImmunology, 2018
Laura E. Johnson, Dirk Brockstedt, Meredith Leong, Peter Lauer, Erin Theisen, John-Demian Sauer, Douglas G. McNeel
Six- to ten-week old A2/DR1 mice were immunized two to four times at 1–3 week intervals (1 week intervals in tumor-bearing animals, and two immunizations 3 weeks apart for non tumor-bearing animal studies) using a DNA vaccine and/or a live, attenuated Listeria monocytogenes (Lm) vaccine. Specifically, a DNA vaccine encoding human prostatic acid phosphatase, pTVG-HP, used for immunization was described previously.19 Immunization was performed intradermally two to four times with 100 µg of pTVG-HP at intervals as indicated. A2/DR1 mice were immunized intraperitoneally up to two times 21 days apart with 5× 106 cfu of LADD-PAP. Control vaccines included a DNA vector not encoding PAP (pTVG4) or a Lm parental strain not encoding PAP (LADD-empty). One week after the last immunization, mice were euthanized and spleens were collected for immunological analysis. Where described, A2/DR1 mice were intravenously injected once with 250 µg anti-mouse CD20 (clone SA271G2, Biolegend) nine days before the first vaccination.to deplete B lymphocytes.