Prostate cancer immunotherapy, particularly in combination with androgen deprivation or radiation treatment. Customized pharmacogenomic approaches to overcome immunotherapy cancer resistance

Alberti, C

doi:10.11138/gchir/2016.37.5.225

Cited by 7 publications

(10 citation statements)

References 96 publications

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“…The first attempts to use nivolumab as a monotherapy in PC patients were not very promising. In three independent clinical trials, no objective clinical response was found in a total of 27 PC patients [7,12,19,23,24,25,29,32]. This could have been caused by an unconfirmed increased expression of PD-L1 on cancer cells in these patients (<5% PD-L1 positive cells) [19,23,24].…”

Section: Impact Of Monoclonal Antibodies Directed Against Immune Checmentioning

confidence: 98%

“…Nivolumab (anti-PD-1 monoclonal antibody) and Iplimumab (anti-CTLA4 monoclonal antibody) have already been approved for the treatment of kidney cancer, non-small cell lung cancer and melanoma [2,4,17,28,29,30]. Clinical trials of ipilimumab in advanced PC are also being carried out [4,5,7,15,21]. In phase I / II trial in 50 patients with metastatic castration-resistant PC (mCRPC) investigating ipilimumab showed a PSA decline of 50% PSA in 8 patients [31].…”

Section: Impact Of Monoclonal Antibodies Directed Against Immune Checmentioning

confidence: 99%

“…Subsequent studies suggest that the most effective strategy in the treatment of mCRPC may be the combination of immunotherapy with traditional therapy [4,6,7]. Combined anti-androgen ablation with anti-PD1 or anti-CTLA-4 antibodies seems to be particularly interesting [7].…”

Section: Impact Of Monoclonal Antibodies Directed Against Immune Checmentioning

confidence: 99%

“…The most serious clinical problem is that in the course of treatment PC becomes refractory to hormone manipulation, known as metastatic castration-resistant prostate cancer (mCRPC) [2,4]. There are many options for the treatment of mCRPC including docetaxel, abiraterone acetate, enzalutamide, cabazitaxel, radium-223, Sipuleucel-T (the only cancer vaccine approved to treat advanced PC so far) [3,4,5,6,7,8], and radioligand therapy (RLT) directed against prostate-specific membrane antigen PSMA, which could be successfully used as a third line therapy of mCRPC [9,10,11].…”

Section: Introductionmentioning

confidence: 99%

“…PD-L1). This phenomenon is known as 'acquired immunity' [6,7,20]. In this way the PC cells avoid elimination by the host immune system.…”

Section: Introductionmentioning

confidence: 99%

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The role of immune checkpoint inhibitors in prostate cancer

Surdacki¹,

Szudy‐Szczyrek

Gorący

et al. 2019

Ann Agric Environ Med.

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Introduction. Prostate cancer (PC) is the most commonly diagnosed malignant tumour and the third cause of cancer deaths among men in Europe. The treatment of early-stage PC is very effective and in many cases allows achievement of a complete cure, whereas the treatment of metastatic prostate cancer (mPC) is still a huge challenge for clinicians. New therapeutic strategies for mPC are urgently needded. One of the most promising methods of treatment is anticancer immunotherapy including the monoclonal antibodies against immune checkpoint inhibitors. Objectives. To present the potential possibilities of using checkpoint inhibitors blockage in the treatment of mPC, and to overview the results of recent research on immune checkpoint inhibitors in patients with PC. State of knowledge. Recent studies suggest that monoclonal antibodies directed against immune checkpoint inhibitors in combination with traditional therapy may become a breakthrough in the treatment of mPC in the near future. Conclusions. The immunotherapy using monoclonal antibodies against immune checkpoint inhibitors seems to be a new opportunity for patients with advanced PC. The key to achieve the maximum anti-tumour response is to choose the best candidates for this therapy and determine the optimal sequence and combination of drugs. The introduction of immunotherapy as the standard treatment of patients with advanced PC requires further studies.

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Section: Impact Of Monoclonal Antibodies Directed Against Immune Checmentioning

confidence: 98%

Section: Impact Of Monoclonal Antibodies Directed Against Immune Checmentioning

confidence: 99%

Section: Impact Of Monoclonal Antibodies Directed Against Immune Checmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…PD-L1). This phenomenon is known as 'acquired immunity' [6,7,20]. In this way the PC cells avoid elimination by the host immune system.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The role of immune checkpoint inhibitors in prostate cancer

Surdacki¹,

Szudy‐Szczyrek

Gorący

et al. 2019

Ann Agric Environ Med.

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Decreased Survival After Combining Thoracic Irradiation and an Anti-PD-1 Antibody Correlated With Increased T-cell Infiltration Into Cardiac and Lung Tissues

Myers¹,

Lü²

2017

International Journal of Radiation Oncology*Biology*Physics

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Purpose Lung cancer is the leading cause of cancer-related mortality in the United States. Radiation, a common component of treatment, can cause acute damage to critical organs including the lungs and the heart, but the serious toxicities from radiotherapy alone is relatively rare. A recent addition to the treatment regimen is immunotherapy, such as anti-PD-1 antibody, which blocks the inhibition of activated T cells. Combining anti-PD-1 treatment and thoracic radiation has potential for improving the outcomes of locally advanced lung cancer over traditional chemoradiation regimens, but the effect of combining these therapies on non-malignant lung tissue has not yet been investigated in preclinical models. Materials and Methods 6–8 week old C57Bl/6 mice were treated with either anti-PD-1 antibody or control IgG with or without thoracic radiation (20Gy), and survival was monitored as an end point to determine any potential increase of toxicity from the combination therapy. Immune cell infiltration into the irradiated cardiac and lung tissues was analyzed via flow cytometry and histologically. Results At 21 days post-radiation, 70% of animals in the IgG + radiation group survived, significantly more than the anti-PD-1 + radiation group (36%; p=0.0169). T cell counts were significantly elevated in both cardiac and pulmonary tissues after combination therapy as compared to anti-PD-1 antibody alone (heart: 6.1 vs 22.4, p<0.001; lung 3.4 vs 20.8, p<0.001) or control IgG plus radiation (heart 11.3 vs 22.4, p<0.05; lung 12.2 vs 20.8, p<0.05) in flow cytometric studies. Histologic analysis confirmed this increase in the comparison of anti-PD-1 antibody alone versus antibody plus irradiation (heart: 464 vs 679 cells per field, p<0.001; lung: 780 vs 1109, p<0.001) and control IgG plus radiation or combination therapy (heart: 526 vs 679 cells per field, p<0.001; lung: 848 vs 1109, p<0.05). Conclusions Combining anti-PD-1 antibody and thoracic irradiation results in T cell infiltration into lung and heart tissue and increases mortality in a preclinical model. We conclude that healthy tissue damaged by irradiation is more susceptible to further damage by activated T cells.

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Alloreactive cytotoxic T lymphocyte immunotherapy treatment of a patient with metastatic prostate cancer

Shi¹,

Chen

et al. 2018

Medicine

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Rationale:Cytotoxic T lymphocyte (CTL) immunotherapy is an autologous cellular immune therapy that has been approved for treating patients with malignant tumors. However, there is still limited information regarding the impact of CTL on metastatic prostate cancer (PC) patients with bone metastatic lesions.Patient concerns:An 82-year-old male patient complained of interrupted urination, urination pain, and significant dysuria on November 24, 2014. Transurethral resection of the prostate (TURP) and postoperative pathological examination showed prostatic adenocarcinoma, and a SPECT/CT scan demonstrated multiple bone metastases. In addition, prostate specific antigen (PSA) and free PSA (FPSA) levels were 54.54 μg/mL and 2.63 μg/mL, respectively, at the beginning of treatment.Diagnoses:The man was diagnosed with prostatic adenocarcinoma and multiple bone metastases.Interventions:The patient received 30 cycles of alloreactive CTL (ACTL) immunotherapy regularly.Outcomes:Over the course of the 2-year treatment, the PC patient exhibited diminished bone metastasis accompanied by a marked reduction of serum PSA and FPSA from 54.54 and 2.63 μg/ml to 0.003 and <0.006 μg/ml, respectively.Lessons:Our clinical observations demonstrate that CTL immunotherapy is a viable treatment option for PC patients, particularly those with bone metastatic lesions and high serum levels of PSA and FPSA.

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Prostate cancer immunotherapy, particularly in combination with androgen deprivation or radiation treatment. Customized pharmacogenomic approaches to overcome immunotherapy cancer resistance

Cited by 7 publications

References 96 publications

The role of immune checkpoint inhibitors in prostate cancer

The role of immune checkpoint inhibitors in prostate cancer

Decreased Survival After Combining Thoracic Irradiation and an Anti-PD-1 Antibody Correlated With Increased T-cell Infiltration Into Cardiac and Lung Tissues

Alloreactive cytotoxic T lymphocyte immunotherapy treatment of a patient with metastatic prostate cancer

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