The Lack of Predictors for Rapid Progression in Prostate Cancer Patients Receiving Sipuleucel-T

Ng, Laura W.; Heck, Wendy; Lavsa, Stacey M.; Crowther, David M.; Atkinson, Brad; Xiao, Lianchun; Araujo, John C.

doi:10.3390/cancers5020511

Cited by 3 publications

(4 citation statements)

References 12 publications

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“…The treatment consists of ex vivo stimulation of DCs with PA2024 that is a fusion protein of prostatic acid phosphatizes (TAA present in 95% of this type of tumor) and GM-CSF. The Phase III clinical trial revealed increased overall survival of patients treated with Provenge in comparison to placebo ( 86 , 87 ).…”

Section: Dc-based Cancer Immunotherapymentioning

confidence: 99%

Immature, Semi-Mature, and Fully Mature Dendritic Cells: Toward a DC-Cancer Cells Interface That Augments Anticancer Immunity

et al. 2013

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Dendritic cells (DCs) are the sentinel antigen-presenting cells of the immune system; such that their productive interface with the dying cancer cells is crucial for proper communication of the “non-self” status of cancer cells to the adaptive immune system. Efficiency and the ultimate success of such a communication hinges upon the maturation status of the DCs, attained following their interaction with cancer cells. Immature DCs facilitate tolerance toward cancer cells (observed for many apoptotic inducers) while fully mature DCs can strongly promote anticancer immunity if they secrete the correct combinations of cytokines [observed when DCs interact with cancer cells undergoing immunogenic cell death (ICD)]. However, an intermediate population of DC maturation, called semi-mature DCs exists, which can potentiate either tolerogenicity or pro-tumorigenic responses (as happens in the case of certain chemotherapeutics and agents exerting ambivalent immune reactions). Specific combinations of DC phenotypic markers, DC-derived cytokines/chemokines, dying cancer cell-derived danger signals, and other less characterized entities (e.g., exosomes) can define the nature and evolution of the DC maturation state. In the present review, we discuss these different maturation states of DCs, how they might be attained and which anticancer agents or cell death modalities (e.g., tolerogenic cell death vs. ICD) may regulate these states.

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Section: Dc-based Cancer Immunotherapymentioning

confidence: 99%

Immature, Semi-Mature, and Fully Mature Dendritic Cells: Toward a DC-Cancer Cells Interface That Augments Anticancer Immunity

et al. 2013

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“…233,238,256,262,263 As for the main oncological indications investigating in this context, 7 trials enrolled melanoma patients, 226,230,236,238,250,251 4 subjects with pancreatic carcinoma, 220,227,228,248 4 women with breast carcinoma, 222,255,258,260 4 patients with various brain tumors, including glioblastoma; 234,242,249,252 3 ovarian carcinoma patients, 229,235 and the others a broad panel of hematological and solid neoplasms. 221,224,225,[231][232][233]237,[239][240][241]243,244,246,247,253,254,256,257,259,261 Taken together, the results of these studies (the majority of which was Phase I or II trials) indicate that DC-based anticancer interventions are generally well tolerated and elicit anticancer immune responses that, at least in a fraction of patients, underpin objective c...…”

Section: Literature Updatementioning

confidence: 94%

“…260,261 In many instances, DCs were employed as standalone therapeutic agents, i.e., administered in the presence of standard adjuvants only. [221][222][223][224][225]229,232,234,240,243,245,246,[249][250][251] Alternatively, DC-based interventions were administered together with cytokine-induced killer (CIK) cells, 220,233,247,[252][253][254][255] adoptively transferred T lymphocytes, 226,236,239,248,256,259 chemotherapy, 227,228,237 immunostimulatory cytokines, 230,235,242 TLR agonists, 257 or radiation therapy. 233,238,256,262,263 As for the main oncological indications investigating in this context, 7 trials enrolled melanoma patients, 226,230,236,238,250,…”

Section: Literature Updatementioning

confidence: 99%

Trial watch: Dendritic cell-based anticancer therapy

et al. 2014

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The use of patient-derived dendritic cells (DCs) as a means to elicit therapeutically relevant immune responses in cancer patients has been extensively investigated throughout the past decade. In this context, DCs are generally expanded, exposed to autologous tumor cell lysates or loaded with specific tumor-associated antigens (TAAs), and then reintroduced into patients, often in combination with one or more immunostimulatory agents. As an alternative, TAAs are targeted to DCs by means of monoclonal antibodies, carbohydrate moieties or viral vectors specific for DC receptors. All these approaches have been shown to (re)activate tumor-specific immune responses in mice, often mediating robust therapeutic effects. In 2010, the first DC-based preparation (sipuleucel-T, also known as Provenge®) has been approved by the US Food and Drug Administration (FDA) for use in humans. Reflecting the central position occupied by DCs in the regulation of immunological tolerance and adaptive immunity, the interest in harnessing them for the development of novel immunotherapeutic anticancer regimens remains high. Here, we summarize recent advances in the preclinical and clinical development of DC-based anticancer therapeutics.

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“…As of 2019, 30 000 men have been prescribed sipuleucel-T. 5 With few exceptions, including 1 institutional retrospective review (36 patients treated with sipuleucel-T) and a clinical trial of androgen-dependent prostate cancer (117 patients treated with sipuleucel-T), 6,7 most of the safety information in the literature [8][9][10][11] is limited to review articles that refer to the clinical trials originally submitted in support of product approval. [12][13][14] We sought to summarize the safety experience of sipuleucel-T in the postmarketing period by assessing US reports submitted to the FDA's Adverse Event Reporting System (FAERS).…”

Section: Introductionmentioning

confidence: 99%

Adverse Events Associated With the Use of Sipuleucel-T Reported to the US Food and Drug Administration’s Adverse Event Reporting System, 2010-2017

2019

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Key Points Question What is the postmarketing safety profile of sipuleucel-T in the United States? Findings The US Food and Drug Administration’s Adverse Event Reporting System received 3216 reports for sipuleucel-T from 2010 through 2017. This case series study identified disproportionate reporting for infusion-associated reactions, infections, certain thromboembolic events, and transient ischemic attacks. Meaning The spectrum of adverse events reported for sipuleucel-T was consistent with the safety experience described in clinical studies and the package insert, and no new safety concerns were identified.

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The Lack of Predictors for Rapid Progression in Prostate Cancer Patients Receiving Sipuleucel-T

Cited by 3 publications

References 12 publications

Immature, Semi-Mature, and Fully Mature Dendritic Cells: Toward a DC-Cancer Cells Interface That Augments Anticancer Immunity

Immature, Semi-Mature, and Fully Mature Dendritic Cells: Toward a DC-Cancer Cells Interface That Augments Anticancer Immunity

Trial watch: Dendritic cell-based anticancer therapy

Adverse Events Associated With the Use of Sipuleucel-T Reported to the US Food and Drug Administration’s Adverse Event Reporting System, 2010-2017

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