Vaccination of Metastatic Melanoma Patients With Autologous Tumor-Derived Heat Shock Protein gp96-Peptide Complexes: Clinical and Immunologic Findings

Belli, Filiberto; Testori, Alessandro; Rivoltini, Licia; Maio, Michele; Andreola, Giovanna; Sertoli, Mario Roberto; Gallino, G.; Piris, Adriano; Cattelan, Anna María; Lazzari, I.; Carrabba, Matteo Giovanni; Scita, Giorgio; Santantonio, Cristina; Pilla, Lorenzo; Tragni, Gabrina; Lombardo, Claudia; Arienti, Flavio; Marchianò, Alfonso; Queirolo, Paola; Bertolini, Francesco; Cova, Agata; Lamaj, Elda; Ascani, L.; Camerini, Roberto; Corsi, Marco; Cascinelli, Natale; Lewis, Jonathan J.; Srivastava, Pramod K.; Parmiani, Giorgio

doi:10.1200/jco.2002.09.134

Cited by 344 publications

(224 citation statements)

References 28 publications

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“…Mutated antigens appeared to be among the preferred targets (33)(34)(35)(36). Although their identification is currently not feasible in a large number of patients, the vaccination of patients with autologous tumor material such as whole tumor cells (37), heat shock proteins (38), and amplified RNA (39) is based on their existence.…”

Section: Discussionmentioning

confidence: 99%

The response of autologous T cells to a human melanoma is dominated by mutated neoantigens

Lennerz

Fatho²,

Gentilini³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

418

318

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Our understanding of pathways leading to antitumor immunity may depend on an undistorted knowledge of the primary antigenic targets of patients' autologous T cell responses. In the melanoma model derived from patient DT, we applied cryopreserved shortterm autologous mixed lymphocyte-tumor cell cultures (MLTCs) in combination with an IFN-␥ enzyme-linked immunospot (ELISPOT) assay to cDNA expression screening. We identified three previously unknown peptides processed from melanosomal proteins tyrosinase (presented by HLA-A*2601 and -B*3801) and gp100 (presented by HLA-B*07021) and five neoantigens generated by somatic point mutations in the patient's melanoma. The mutations were found in the genes SIRT2, GPNMB, SNRP116, SNRPD1, and RBAF600. Peptides containing the mutated residues were presented by HLA-A*03011, -B*07021, and -B*3801. Mutation-induced functional impairment was so far demonstrated for SIRT2. Within MLTC responder populations that were independently expanded from the patient's peripheral blood lymphocytes of different years, T cells against mutated epitopes clearly predominated. These results document a high degree of individuality for the cellular antitumor response and support the need for individualizing the monitoring and therapeutic approaches to the primary targets of the autologous T cell response, which may finally lead to a more effective cancer immunotherapy.expression cloning ͉ peptide ͉ tumor antigen ͉ mixed lymphocyte-tumor cell culture ͉ cytotoxic T lymphocytes

show abstract

Section: Discussionmentioning

confidence: 99%

The response of autologous T cells to a human melanoma is dominated by mutated neoantigens

Lennerz

Fatho²,

Gentilini³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

418

318

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show abstract

“…39; C. Castelli, unpublished data). The ability of tumor-derived Gp96 to induce a tumor-specific response in vivo when used as a vaccine has been confirmed in metastatic melanoma and colorectal cancer patients (57,58). However, due to the intrinsic difficulties in obtaining enough autologous tumor cells, the ability of boosting in vivo T cell responses directed against unique Ags still remains to be fully documented in the human HSP system.…”

Section: Implications For Immunotherapymentioning

confidence: 99%

Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials

Parmiani

Filippo

Novellino

et al. 2007

The Journal of Immunology

Self Cite

146

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The individual, unique tumor Ags, which characterize each single tumor, were described 50 years ago in rodents but their molecular characterization was limited to few of them and obtained during the last 20 years. Here we summarize the evidence for the existence and the biological role of such Ags in human tumors, although such evidence was provided only during the last 10 years and by a limited number of studies, a fact leading to a misrepresentation of unique Ags in human tumor immunology. This was also due to the increasing knowledge on the shared, self-human tumor Ags, which have been extensively used as cancer vaccines. In this review, we highlight the biological and clinical importance of unique Ags and suggest how they could be used in clinical studies aimed at assessing their immunogenic and clinical potential both in active and adoptive immunotherapy of human tumors.

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“…22 Freshly isolated peripheral blood mononuclear cells (PBMC) were added at 3ϫ10 5 cells per well (in triplicate) with 20 g/mL of CMLVAX100 peptides or control peptides (HIV-derived HLA A3 and A11 binder peptides, RAS peptide). The AEC (3-amino-9-ethylcarbazole) staining kit (Sigma, St Louis, MO, USA) was used for colorimetric revelation of spots in the dark, and the number of spots was counted by use of an automated image analysis ELISPOT reader system (AELVIS reader system, Thornwood, NY, USA).…”

Section: Specific Immunological Assessmentmentioning

confidence: 99%

Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial

et al. 2005

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Vaccination of Metastatic Melanoma Patients With Autologous Tumor-Derived Heat Shock Protein gp96-Peptide Complexes: Clinical and Immunologic Findings

Abstract: Vaccination of metastatic melanoma patients with autologous HSPPC-96 is feasible and devoid of significant toxicity. This vaccine induced clinical and tumor-specific T-cell responses in a significant minority of patients.

Cited by 344 publications

References 28 publications

The response of autologous T cells to a human melanoma is dominated by mutated neoantigens

The response of autologous T cells to a human melanoma is dominated by mutated neoantigens

Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials

Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial

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