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Expert Review of Anticancer Therapy Dec 2013Immunotherapy with cytokines was the first effective treatment in metastatic renal cell carcinoma (mRCC). Long-term responders and complete remissions were observed, but... (Review)
Review
Immunotherapy with cytokines was the first effective treatment in metastatic renal cell carcinoma (mRCC). Long-term responders and complete remissions were observed, but efficacy in the overall population was limited with the consequence that targeted agents replaced cytokines. The discovery of tumor associated antigens as direct targets paved the way from theses rather unspecific to specific immunotherapeutic strategies, which are discussed in this review. Autologous or dendritic cell (DC) based tumor vaccination with vitespen or AGS-003, adoptive T-cell transfer and synthetic peptide vaccination with IMA901 are new and promising approaches. Besides that the more passive strategies of antibody dependent cytotoxicity with the VEGF antibody bevacizumab or the carbonic anhydrase IX antibody girentuximab are discussed. Immunomodulation by cyclophosphamide, tyrosine kinase inhibitors or nivolumab, which targets the PD-1 axis, further promote T-cell activation and combinatory strategies with these agents are outlined.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antigens, Neoplasm; Bevacizumab; Cancer Vaccines; Carcinoma, Renal Cell; Dendritic Cells; Humans; Immunotherapy; Kidney Neoplasms; T-Lymphocytes
PubMed: 24215158
DOI: 10.1586/14737140.2013.856761 -
International Journal of Cancer May 2012The passive administration of specific antibodies that selectively target tumors is a well-known strategy in cancer treatment. Active immunotherapy using peptide... (Review)
Review
The passive administration of specific antibodies that selectively target tumors is a well-known strategy in cancer treatment. Active immunotherapy using peptide vaccines, in contrast, is expected to induce specific, cytolytic T cells in the patient, which react against tumor antigens and destroy malignant cells. Although several concepts exist, the identification and low immunogenicity of tumor-specific peptides remain a serious problem. Heat shock proteins (HSPs), notably glycoprotein (Gp) 96, are of special interest, because they are able to take molecular peptide-fingerprints of the protein array characteristic for a particular cell. Association of Gp96 with peptides has been shown to be essential for crosspresentation and activation of T cells. Consequently, Gp96-peptide complexes extracted from cancer cells harbor the tumor-specific peptides and are immunogenic, thus offering a tool for active immunization against the tumor. Already, several immunotherapy studies of human cancers have been carried out, showing no severe adverse effects but unfortunately only limited improvement in the clinical outcome. Vitespen, a commercial HSP-peptide complex vaccine based on tumor-derived Gp96, seems to induce an improved overall survival for subsets of early stage melanoma and kidney cancer patients. The limited access to vaccine material derived from the autologous tumor requires the development of alternative protocols. Moreover, counteracting immunosuppressive mechanisms induced by the malignancy might further improve the efficacy of vaccinations. This review critically analyzes the current state of clinical immunotherapy with Gp96, with special attention to Vitespen.
Topics: Animals; Cancer Vaccines; Clinical Trials as Topic; Heat-Shock Proteins; Humans; Immunotherapy, Active; Monitoring, Immunologic; Neoplasms
PubMed: 22052568
DOI: 10.1002/ijc.27332 -
Expert Review of Vaccines Nov 2009Heat-shock proteins are highly conserved, stress-induced proteins with chaperone function for trafficking and delivering peptides within the different compartments of... (Review)
Review
Heat-shock proteins are highly conserved, stress-induced proteins with chaperone function for trafficking and delivering peptides within the different compartments of the cell. Tumor-derived heat-shock protein-peptide complexes (HSPPCs) can be used for vaccination against malignancies. In particular, the HSPPC-96-based vaccine vitespen (formerly Oncophage) is the first autologous cancer vaccine made from individual patients' tumors that has shown encouraging results in clinical trials. In Phase I and II clinical trials, this vaccine has shown activity on different malignancies, such as gastric cancer, colorectal cancer, pancreatic cancer, non-Hodgkin's lymphoma and chronic myelogenous leukemia. In Phase III clinical trials in melanoma and kidney cancer, it demonstrated an excellent safety profile with almost no toxicity. Heat-shock protein-based vaccines can be considered as a novel therapeutic approach with a promising role in cancer management.
Topics: Cancer Vaccines; Clinical Trials, Phase III as Topic; Heat-Shock Proteins; Humans; Kidney Neoplasms; Melanoma
PubMed: 19863242
DOI: 10.1586/erv.09.108 -
Future Oncology (London, England) Aug 2009Vitespen is a heat shock protein (gp96)-peptide complex purified from resected autologous tumors, developed as a means of capturing the antigenic 'fingerprint' of a... (Review)
Review
Vitespen is a heat shock protein (gp96)-peptide complex purified from resected autologous tumors, developed as a means of capturing the antigenic 'fingerprint' of a specific cancer for use as a patient-specific vaccine. Vitespen has been extensively assessed in animal models, and clinically in a range of cancers, including Phase I and II trials in colorectal cancer, glioblastoma, lung cancer, melanoma and renal cell carcinoma, and two Phase III studies in melanoma and renal cell carcinoma. Vitespen has shown itself capable of inducing major histocompatibility class I-restricted immune responses in a range of tumor types, and clinical responses in patients with earlier-stage disease, in line with previously published data on cancer vaccines. Vitespen is almost devoid of side effects aside from minor injection-site reactions.
Topics: Animals; Cancer Vaccines; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Evaluation, Preclinical; Heat-Shock Proteins; Humans; Mice; Neoplasms
PubMed: 19663726
DOI: 10.2217/fon.09.46 -
Methods and Findings in Experimental... Apr 2009(+)-Dapoxetine hydrochloride, [(123)I]-BZA, 9-Aminocamptothecin; Abacavir sulfate/lamivudine, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Alvocidib hydrochloride,...
(+)-Dapoxetine hydrochloride, [(123)I]-BZA, 9-Aminocamptothecin; Abacavir sulfate/lamivudine, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Alvocidib hydrochloride, Ambrisentan, Amsilarotene, Anacetrapib, Anakinra, Apricitabine, Aripiprazole, Arsenic trioxide, Atazanavir sulfate, Atazanavir/ritonavir, Atrasentan, Azacitidine; Banoxantrone, Bazedoxifene acetate, Bevacizumab, Bexarotene, Biphasic insulin aspart, Bortezomib, Bosentan, Bromfenac; Cachectin, Calcipotriol/betamethasone dipropionate, Canakinumab, Carfilzomib, CAT-354, CCX-282, Certolizumab pegol, Cetuximab, Choline fenofibrate, Clevudine, Clofarabine, CNTO-328, Corifollitropin alfa, Crofelemer; Daptomycin, Darbepoetin alfa, Darunavir, Dasatinib, Decitabine, Deferasirox, Denosumab, Duloxetine hydrochloride, Dutasteride; Emtricitabine, Enfuvirtide, Entecavir, Epoetin zeta, Erlotinib hydrochloride, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Farglitazar, Febuxostat, Fosamprenavir calcium, FX-06; Gabapentin enacarbil, Gefitinib; HIVIS DNA; Imatinib mesylate, INCB- 18424, Indacaterol, Inotuzumab ozogamicin, Insulin detemir; JNJ-26854165; Lacosamide, Landiolol, Laromustine, Lenalidomide, Liposomal doxorubicin, L-NAME, Lopinavir, Lopinavir/ritonavir, Lumiracoxib; Maraviroc, Mepolizumab, Methoxy polyethylene glycol- epoetin-beta, Miglustat, MK-0493, MVA-CMDR, Mycophenolic acid sodium salt; Natalizumab, Nepafenac, Neratinib, Neridronic acid, Nesiritide, Nilotinib hydrochloride monohydrate; Olmesartan medoxomil, Omacetaxine mepesuccinate, Omalizumab; Paclitaxel poliglumex, Palifermin, Patupilone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, PHA-848125, Pitavastatin calcium, Posaconazole, Povidone-iodine liposome complex, Prasugrel, Pregabalin, Prucalopride; Raltegravir potassium, Retigabine, Revaprazan hydrochloride, rhFSH, Rilpivirine, Rivaroxaban, Romidepsin, Rosuvastatin calcium, RWJ-676070; SAR-109659, Sitagliptin phosphate monohydrate, Sorafenib, Stavudine/Lamivudine/Nevirapine, Sunitinib malate; Tadalafil, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tenofovir disoproxil fumarate/emtricitabine/efavirenz, Teriparatide, Tigecycline, Tiotropium bromide, Tipifarnib, Tipranavir, Tocilizumab, Trifluridine/TPI; UP-780; Vandetanib, Vardenafil hydrochloride hydrate, Vatalanib succinate, Vitespen, Vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate.
Topics: Clinical Trials as Topic; Humans
PubMed: 19536362
DOI: No ID Found -
European Urology Jun 2009Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans. Although immunotherapy is currently much less used than in the past, it remains an... (Review)
Review
CONTEXT
Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans. Although immunotherapy is currently much less used than in the past, it remains an important option that warrants further exploration.
OBJECTIVE
To examine the current status of vaccine therapy for RCC and to provide information on relevant clinical studies.
EVIDENCE ACQUISITION
We reviewed recent literature on Medline (2003-2008, using the keywords renal cell carcinoma, cancer vaccines, active immunotherapy, and dendritic cells). Subsequent references were identified from reference list of retrieved articles. Quality assessment included prospective phase 1-3 trials and critical evaluations with low numbers of patients.
EVIDENCE SYNTHESIS
Therapeutic vaccines can be divided in autologous tumour cell-based vaccines, genetically modified tumour cell-based and dendritic cell (DC)-based vaccines, and peptide-based vaccines. To date, only two randomised, adjuvant, phase 3 studies investigating RCC vaccines have been published. Autologous tumour cell vaccine (Reniale) improved the 5-yr progression-free survival (PFS) for high-risk nonmetastatic RCC patients at all tumour stages when administered after nephrectomy. The benefit was clearer in the T3 group. A per-protocol analysis revealed a statistically significant PFS and overall survival (OS) in favour of the vaccine. Autologous tumour-derived heat shock protein peptide complex (HSPPC-96; vitespen) could not significantly improve recurrence-free survival in RCC patients at high risk for recurrence after nephrectomy, but did so in intermediate risk patients. DC vaccination in metastatic RCC (mRCC) patients is safe and can induce antigen-specific immune response and obtain tumour regression in a subset of patients.
CONCLUSIONS
RCC vaccines have much less toxicity than other current therapies and remain an important area for further research. Reniale has shown significant benefit as an adjuvant RCC vaccine. Vitespen seems promising as an adjuvant treatment in earlier stage disease. A possible area of research is the use of RCC vaccines with immune-enhancing or antiangiogenic agents in the adjuvant setting.
Topics: Cancer Vaccines; Carcinoma, Renal Cell; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Kidney Neoplasms; Male; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Survival Rate; Treatment Outcome; Vaccination
PubMed: 19201522
DOI: 10.1016/j.eururo.2009.01.043 -
Nature Clinical Practice. Urology Dec 2008
PubMed: 19002125
DOI: 10.1038/ncpuro1256 -
Expert Opinion on Biological Therapy Dec 2008Heat-shock proteins (HSPs) are a group of proteins whose expression is increased when the cells are exposed to elevated temperatures or other stressful conditions. This... (Review)
Review
Heat-shock proteins (HSPs) are a group of proteins whose expression is increased when the cells are exposed to elevated temperatures or other stressful conditions. This increase in expression is transcriptionally regulated. The function of HSPs is similar in virtually all living organisms, from bacteria to humans. Their expression also occur under non-stressful conditions, simply 'monitoring' the cell's proteins, i.e., they carry old proteins to the cell's 'recycling bin' and they help newly synthesized proteins fold properly. These activities are part of a cell's own repair system. HSPs are molecular chaperones for protein molecules. They are usually cytoplasmic proteins and they perform functions in various intracellular processes. Tumour-derived HSP-peptide complexes (HSPPCs) can be used for vaccination against malignancies. In particular, HSPPC-96 complex, called Vitespen (formerly Oncophage) is a HSPs-based vaccine made from individual patients' tumours with a promising role in cancer management. This vaccine has been extensively studied in Phase I and II clinical trials, showing activity on different malignancies, including gastric cancer, colorectal cancer, pancreatic cancer, non-Hodgkin's lymphoma and chronic myelogenous leukaemia. The vaccine has also been studied in Phase III clinical trials in melanoma and kidney cancer, showing an excellent safety profile with essentially no toxicity. Thus, HSP-based vaccines are a novel therapeutic approach with a promising role in cancer management.
Topics: Cancer Vaccines; Clinical Trials as Topic; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interferons; Melanoma; Oncolytic Virotherapy
PubMed: 18990084
DOI: 10.1517/14712590802517970 -
Methods and Findings in Experimental... 2008(-)-Epigallocatechin gallate, 501516, 89-12; Abatacept, Adalimumab, Adefovir dipivoxil, AG-701, Agatolimod sodium, Alefacept, Aliskiren fumarate, Apixaban, Atazanavir...
(-)-Epigallocatechin gallate, 501516, 89-12; Abatacept, Adalimumab, Adefovir dipivoxil, AG-701, Agatolimod sodium, Alefacept, Aliskiren fumarate, Apixaban, Atazanavir sulfate, Atrasentan, Axitinib; BI-1744-CL, BIBF-1120, BIBW-2992, Bortezomib; Carboxyamidotriazole, Caspofungin acetate, CBP-501, Cediranib, Ceftobiprole, Certolizumab pegol, Cetuximab, Cholesteryl hydrophobized polysaccharide-Her2 protein complex, CHP-NY-ESO-1, Cypher; Dalbavancin, Dalcetrapib, Daptomycin, Darapladib, Deferasirox, Deforolimus, Denosumab, DNA-HIV-C, Dovitinib, DR-5001, Dronedarone hydrochloride, DT388IL3; E75, EC-17/EC-90, Ecogramostim, Efungumab, Entecavir, EP HIV-1090, EP-2101, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Faropenem daloxate, Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium, Fulvestrant; Golimumab, GSK-089, GW-590735; HO/03/03, hTERT572, hTERT572Y; Iloperidone; Immunoglobulin intravenous (human), Ispinesib mesylate, Istradefylline, Ixabepilone; JR-031, JX-594; KLH; Laropiprant, Lecozotan hydrochloride, Lenalidomide, Lestaurtinib, Linezolid; MGCD-0103, MK-0646, MVA-BN Measles; NI-0401, Niacin/laropiprant, NSC-719239, NYVAC-C; Ospemifene; Paliperidone palmitate, PAN-811, PCV7, Pegfilgrastim, Peginterferon alfa-2a, PEGirinotecan, Perifosine, Pertuzumab, PF-00299804, Picoplatin, Pimavanserin tartrate, Pitavastatin calcium, Pomalidomide, Prasterone, Pratosartan, Prucalopride, PSMA27/pDOM, Pyridoxal phosphate; QS-21, Quercetin; Rebimastat, Rimonabant, Rolofylline, Romidepsin, Rosuvastatin calcium, RTS,S/SBAS2; SCH-530348, SN-29244, Soblidotin, Sodium dichloroacetate, Solifenacin succinate, Sorafenib, Spheramine, SU-6668, Succinobucol; Taranabant, Taxus, Telaprevir, Telavancin hydrochloride, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Tocilizumab, Triphendiol; UC-781, Udenafil, UNIL-025; V-5 Immunitor, Valsartan/amlodipine besylate, Varenicline tartrate, Velafermin, Vernakalant hydrochloride, Vinflunine, Vitespen, Vorinostat, VX-001; Xience V, XRP-0038; Yttrium Y90 Epratuzumab; Z-360, Ziconotide, Ziprasidone hydrochloride, Zotarolimus, Zotarolimus-eluting stent.
Topics: Clinical Trials as Topic; Humans
PubMed: 18850047
DOI: No ID Found -
Methods and Findings in Experimental... Jun 2008(+)-Dapoxetine hydrochloride, (R)-Etodolac; Abatacept, ABT-510, Adalimumab, Agatolimod sodium, Alemtuzumab, Alvocidib hydrochloride, Aminolevulinic acid methyl ester,...
(+)-Dapoxetine hydrochloride, (R)-Etodolac; Abatacept, ABT-510, Adalimumab, Agatolimod sodium, Alemtuzumab, Alvocidib hydrochloride, Aminolevulinic acid methyl ester, Aripiprazole, AS01B, AS02B, AS02V, Azacitidine; Becatecarin, Bevacizumab, Bevirimat, Bortezomib, Bremelanotide; CAIV-T, Canfosfamide hydrochloride, CHR-2797, Ciclesonide, Clevidipine; Darbepoetin alfa, Decitabine, Degarelix acetate, Dendritic cell-based vaccine, Denosumab, Desloratadine, DMXB-Anabaseine, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Eicosapentaenoic acid/docosahexaenoic acid, Eletriptan, Enzastaurin hydrochloride, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Ferumoxytol, Fesoterodine fumarate, Fulvestrant; Gefitinib, GM-CSF DNA, GSK-690693; H5N1 avian flu vaccine, Hepatitis B hyperimmunoglobulin, Human Fibroblast Growth Factor 1, Hypericin-PVP; Icatibant acetate, Iclaprim, Immunoglobulin intravenous (human), Ipilimumab, ISS-1018; L19-IL-2, Lapuleucel-T, Laropiprant, Liposomal doxorubicin, LP-261, Lumiracoxib, LY-518674; MDV-3100, MGCD-0103, Mirabegron, MyoCell; NASHA/Dx, Niacin/laropiprant; O6-Benzylguanine, Ocrelizumab, Olmesartan medoxomil, Omalizumab; P-276-00, Paclitaxel nanoparticles, Paclitaxel nanoparticles, Padoporfin, Paliperidone, PAN-811, Pegaptanib octasodium, Pegfilgrastim, Pemetrexed disodium, PF-00299804, Pimecrolimus, Prasugrel, Pregabalin; Reolysin, Rimonabant, Rivaroxaban, Rosuvastatin calcium; Satraplatin, SCH-697243,Selenite sodium, Silodosin, Sorafenib, Sunitinib malate; Talarozole, Taxus, Temsirolimus, Tocilizumab, Tolevamer potassium sodium, Tremelimumab, TTP-889; Uracil; V-260, Valsartan/amlodipine besylate, Vardenafil hydrochloride hydrate, Varenicline tartrate, Varespladib, Vitespen, Voclosporin, VX-001; Xience V; Zotarolimus-eluting stent.
Topics: Clinical Trials as Topic; Humans
PubMed: 18806898
DOI: No ID Found