Immune checkpoint blockade in cancer treatment: a double-edged sword cross-targeting the host as an "innocent bystander".

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Published in Toxins (Basel) on March 03, 2014

Authors

Lucia Gelao1, Carmen Criscitiello2, Angela Esposito3, Aron Goldhirsch4, Giuseppe Curigliano5

Author Affiliations

1: Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. lucia.gelao@ieo.it.
2: Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. carmen.criscitiello@ieo.it.
3: Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. angela.esposito@ieo.it.
4: Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. aaron.goldhirsch@ieo.it.
5: Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. giuseppe.curigliano@ieo.it.

Associated clinical trials:

Study of Pembrolizumab (MK-3475) in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma (P07990/MK-3475-001/KEYNOTE-001) (KEYNOTE-001) | NCT01295827

Multiple Ascending Dose (MDX1105-01) (Anti-PDL1) | NCT00729664

Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma (CheckMate 067) | NCT01844505

Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) (CheckMate 017) | NCT01642004

Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025) | NCT01668784

Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) (CheckMate 012) | NCT01454102

Safety Study of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors | NCT01968109

Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma | NCT01024231

Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma (CheckMate 066) | NCT01721772

Safety Study of IL-21/Anti-PD-1 Combination in the Treatment of Solid Tumors | NCT01629758

Safety Study of Nivolumab by Itself or in Combination in Patients With Lymphoma or Multiple Myeloma | NCT01592370

Phase 3 Trial in Squamous Non Small Cell Lung Cancer Subjects Comparing Ipilimumab Versus Placebo in Addition to Paclitaxel and Carboplatin | NCT01285609

A Phase 1b Study of Atezolizumab in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Participants With BRAFV600-Mutation Positive Metastatic Melanoma | NCT01656642

Study to Evaluate the Safety and Efficacy of Two Different Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Participants With Advanced Melanoma (MK-3475-006/KEYNOTE-006) | NCT01866319

A Study of Nivolumab by Itself or Nivolumab Combined With Ipilimumab in Patients With Advanced or Metastatic Solid Tumors | NCT01928394

Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-012/KEYNOTE-012) | NCT01848834

Study of Two Doses of MK-3475 (Pembrolizumab) Versus Docetaxel in Previously-Treated Participants With Non-Small Cell Lung Cancer (MK-3475-010/KEYNOTE-010) | NCT01905657

A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors | NCT01633970

Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma | NCT01740297

Tremelimumab and CP-870,893 in Patients With Metastatic Melanoma | NCT01103635

A Study of Atezolizumab in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) [FIR] | NCT01846416

Trial in Extensive-Disease Small Cell Lung Cancer (ED-SCLC) Subjects Comparing Ipilimumab Plus Etoposide and Platinum Therapy to Etoposide and Platinum Therapy Alone | NCT01450761

Efficacy Study of Ipilimumab Versus Placebo to Prevent Recurrence After Complete Resection of High Risk Stage III Melanoma | NCT00636168

Phase II, 2nd Line Melanoma - RAND Monotherapy | NCT00612664

A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab | NCT01975831

Study of Nivolumab (BMS-936558) Plus Ipilimumab Compared With Ipilimumab Alone in the Treatment of Previously Untreated, Unresectable, or Metastatic Melanoma (CheckMate 069) | NCT01927419

Safety Study of BMS-986015 (Anti-KIR) in Combination With Ipilimumab in Subjects With Selected Advanced Tumor | NCT01750580

Study of Dabrafenib +/- Trametinib in Combination With Ipilimumab for V600E/K Mutation Positive Metastatic or Unresectable Melanoma | NCT01767454

Safety, Tolerability, Pharmacokinetics, and Immunoregulatory Study of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Solid Tumors and Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma | NCT01471210

Combination Study of Urelumab and Rituximab in Patients With B-cell Non-Hodgkins Lymphoma | NCT01775631

A Randomized Phase 2 Study of Atezolizumab (an Engineered Anti-PDL1 Antibody) Compared With Docetaxel in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Failed Platinum Therapy - "POPLAR" | NCT01903993

A Phase 1/2 Randomized, Blinded, Placebo Controlled Study of Ipilimumab in Combination With INCB024360 or Placebo in Subjects With Unresectable or Metastatic Melanoma | NCT01604889

Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064) | NCT01783938

The Addition of Ipilimumab to Carboplatin and Etoposide Chemotherapy for Extensive Stage Small Cell Lung Cancer (ICE) | NCT01331525

Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery | NCT01274338

Phase II Safety Study of Vemurafenib Followed by Ipilimumab in Subjects With V600 BRAF Mutated Advanced Melanoma | NCT01673854

Sipuleucel-T and Ipilimumab for Advanced Prostate Cancer | NCT01832870

A Phase 2, Multicenter Study of FOLFIRINOX Followed by Ipilimumab With Allogenic GM-CSF Transfected Pancreatic Tumor Vaccine in the Treatment of Metastatic Pancreatic Cancer | NCT01896869

First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma | NCT01524991

Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma | NCT01689974

Study of Pembrolizumab (MK-3475) Monotherapy in Advanced Solid Tumors and Pembrolizumab Combination Therapy in Advanced Non-small Cell Lung Cancer (MK-3475-011/KEYNOTE-011) | NCT01840579

Dasatinib and Ipilimumab in Treating Patients With Gastrointestinal Stromal Tumors or Other Sarcomas That Cannot Be Removed by Surgery or Are Metastatic | NCT01643278

Ipilimumab in Combination With Androgen Suppression Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer | NCT01498978

Concurrent Ipilimumab and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Melanoma (SART) | NCT01565837

Phase II Study of Ipilimumab Monotherapy in Recurrent Platinum-sensitive Ovarian Cancer | NCT01611558

Chemoradiation Therapy and Ipilimumab in Treating Patients With Locally Advanced Cervical Cancer | NCT01711515

Ipilimumab or Nivolumab in Treating Patients With Relapsed Hematologic Malignancies After Donor Stem Cell Transplant | NCT01822509

Ipilimumab and Imatinib Mesylate in Advanced Cancer | NCT01738139

A Phase Ib Trial of Concurrent Cetuximab (ERBITUX®) and Intensity Modulated Radiotherapy (IMRT) With Ipilimumab (YERVOY®) in Locally Advanced Head and Neck Cancer | NCT01860430

Ipilimumab +/- Vaccine Therapy in Treating Patients With Locally Advanced, Unresectable or Metastatic Pancreatic Cancer | NCT00836407

Tremelimumab With Chemoembolization or Ablation for Liver Cancer | NCT01853618

Ipilimumab and Gemcitabine Hydrochloride in Treating Patients With Stage III-IV or Recurrent Pancreatic Cancer That Cannot Be Removed by Surgery | NCT01473940

Safety Study of IL-21/Ipilimumab Combination in the Treatment of Melanoma | NCT01489059

Ipilimumab, Nivolumab, and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma | NCT01896999

Ipilimumab and Lenalidomide in Advanced Cancer | NCT01750983

Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma (Tremelimumab) | NCT01843374

NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma | NCT01810016

Granulocyte Macrophage-Colony Stimulating Factor and Ipilimumab as Therapy in Melanoma (GIPI) | NCT01363206

Vaccine Therapy With or Without Recombinant Interleukin-12 Followed by Daclizumab in Treating Patients With Metastatic Melanoma | NCT01307618

Ipilimumab and Rituximab in Treating Patients With Relapsed or Refractory B-cell Lymphoma | NCT01729806

Doxycycline, Temozolomide and Ipilimumab in Melanoma | NCT01590082

HD IL-2 + Ipilimumab in Patients With Metastatic Melanoma (PROCLIVITY 02) | NCT01856023

Phase II Study of Abraxane Plus Ipilimumab in Patients With Metastatic Melanoma | NCT01827111

Yttrium-90-labeled Daclizumab With Chemotherapy and Stem Cell Transplant for Hodgkin s Lymphoma | NCT01468311

Clinical Evaluation of Yervoy in Combination With Adoptive T Cell Transfer for Metastatic Melanoma Patients | NCT01988077

Neoadjuvant Combination Therapy With Ipilimumab and HighDose IFN-α2b for Melanoma | NCT01608594

Ipilimumab With Carboplatin and Paclitaxel in Patients With Unresectable Stage III and Stage IV Melanoma | NCT01676649

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