Induction of Immune Responses and Clinical Efficacy in a Phase II Trial of IDM-2101, a 10-Epitope Cytotoxic T-Lymphocyte Vaccine, in Metastatic Non–Small-Cell Lung Cancer

Barve, Minal; Bender, James; Senzer, Neil; Cunningham, Casey; Greco, F. Anthony; McCune, David; Steis, Ronald G.; Khong, Hung T.; Richards, Donald A.; Stephenson, Joe; Ganesa, Prasanthi; Nemunaitis, J.; Ishioka, Glenn; Pappen, Beena O.; Nemunaitis, Michael; Morse, Michael A.; Mills, Bonnie; Maples, Phillip B.; Sherman, Jeffrey; Nemunaitis, John

doi:10.1200/jco.2008.16.6462

Cited by 86 publications

(49 citation statements)

References 51 publications

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“…While single MHC class I-restricted TAA and mycobacterium tuberculosis (MTb) 26 microbial antigenderived peptides showed promising preclinical results, both in vitro and in vivo, [27][28][29] they have demonstrated limited clinical efficacy. 30 This outcome was suggested to reflect the limited polyclonal cytotoxic CD8 C T-cell antigenic repertoire as well as the inadequate pan-MHC response, 31 mediated by MHC class II-restricted CD4 C T-helper epitope(s). The absence of MHC class II epitopes was shown to induce immunological tolerance 32 to immunizing antigens, rather than long lasting CD8 C T-cell activationassociated immunity.…”

Section: The Advantages Of Sp Domains As Peptide-based Vaccinesmentioning

confidence: 99%

The use of signal peptide domains as vaccine candidates

Kovjazin¹,

Carmon²

2014

Human Vaccines & Immunotherapeutics

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Section: The Advantages Of Sp Domains As Peptide-based Vaccinesmentioning

confidence: 99%

The use of signal peptide domains as vaccine candidates

Kovjazin¹,

Carmon²

2014

Human Vaccines & Immunotherapeutics

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“…21,22 It also has been evaluated for clinical efficacy in phase 2 trials in NSCLC patients. 38 The IDM-2101 vaccine was designed to induce CTLs against 5 TAAs that frequently are overexpressed in NSCLC (ie, carcinoembryonic antigen, p53, HER-2/neu, and the melanoma antigens MAGE-2 and MAGE-3). IDM-2101 is composed of 10 synthetic peptides from these TAAs, 9 of which represent CTL epitopes.…”

Section: Clinical Trials Using Polyepitope Long-peptide Vaccinesmentioning

confidence: 99%

“…39 In a phase 2 study, patients initially achieved stable disease, but overall survival was comparable to that of historic patients who received conventional treatment. 38 A novel melanoma vaccine comprised of 6 melanoma-associated peptides as antigenic targets for melanoma-reactive T h cells was evaluated for safety and immunogenicity in a phase 1/2 trial. 40 Vaccination with the helper peptide vaccine was well tolerated.…”

Section: Clinical Trials Using Polyepitope Long-peptide Vaccinesmentioning

confidence: 99%

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

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The use of synthetic peptides as vaccines aimed at the induction of therapeutic CD8-positive T-cell responses against tumor cells initially experienced great enthusiasm, mostly because of advances in vaccine technology, including design, synthesis, and delivery. However, despite impressive results in animal models, the application of such vaccines in humans has met with only limited success. The therapeutic activity of vaccine-stimulated, tumor-specific, CD8-positive T cells can be hampered through the physical burden of the tumor, tolerance mechanisms, and local factors within the tumor microenvironment. Recently, accumulating evidence has suggested that combining a peptide-based therapeutic vaccination with conventional chemotherapy can uncover the full potential of the antitumor immune response, increasing the success of immunotherapy. In addition, therapeutic vaccination in the preventive setting has been extremely effective in eliciting antitumor responses in preclinical tumor models and has demonstrated good promise clinically in patients with minimal residual disease. The rationale behind preventive vaccination is that patients with minimal tumor burden still have a fully competent immune system capable of developing robust antitumor responses. Finally, therapeutic CD8-positive T-cell peptide vaccines have been improved by coimmunization with T-helper epitopes expressed on long peptides.

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“…CpG ODN accelerated the induction of protective antibodies and generated higher and more persistent antibody titers with protein vaccines (26). Peptide based vaccines by themselves generally failed to elicit strong immune responses (27)(28)(29)(30). In an early phase I trial that focused on CpG ODN as an adjuvant, 10-fold more antigen specific T cells were generated by patients with malignant melanoma immunized with the vaccine containing CpG versus the same vaccine lacking CpG (31).…”

Section: Discussionmentioning

confidence: 99%

CpG oligodeoxynucleotides augment antitumor efficacy of folate receptor α based DNA vaccine

et al. 2017

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Abstract. Folate receptor α (FRα) is overexpressed in a variety of solid tumors and has become an attractive target antigen for immunotherapy purposes. A DNA vaccine was generated by ligation of FRα cDNA into the eukaryotic vector pcDNA3.1. Expression of FRα was confirmed in transiently transfected B16 cells. B16 cell lines that stably express FRα were set up by G418 selection. A total of 100 µg purified plasmid DNA alone or in combination with CpG oligodeoxynucleotides (CpG ODN) was injected intramuscularly in C57BL/6 mice four times at one week intervals. ELISA analysis confirmed that high titers of antibodies against FRα existed in the sera of the experimental animals. Specific cytotoxic T lymphocyte activity against FRα-expressing B16 cells was found and FRα specific lymphocyte proliferation was detected. Coinjection of CpG ODN increased both humoral and cellular immune responses. In the protective model, in which C57BL/6 mice were immunized with the FRα DNA vaccine four weeks before tumor cell inoculation, the growth of tumor was significantly inhibited, and the presence of CpG ODN further increased the inhibitory effect. FRα DNA vaccine alone did not show a significant inhibitory effect in the therapeutic model, in which the DNA vaccine was immediately injected after tumor inoculation. However, FRα DNA vaccine plus CpG ODN showed a significant inhibitory effect in tumor growth. Survival curves for both animal experiments confirmed that mice immunized with pcDNA3.1/FRα plus CpG ODN had a significantly prolonged survival period than that of the pcDNA3.1 control group, the CpG ODN group or the pcDNA3.1/FRα group. The above showed that human FRα based DNA vaccination with CpG ODN as an adjuvant was effective in growth inhibition of a FRα expressing tumor in mice and deserves further evaluation as a possible immunotherapy.

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Induction of Immune Responses and Clinical Efficacy in a Phase II Trial of IDM-2101, a 10-Epitope Cytotoxic T-Lymphocyte Vaccine, in Metastatic Non–Small-Cell Lung Cancer

Abstract: IDM-2101 was well tolerated, and evidence of efficacy was suggested.

Cited by 86 publications

References 51 publications

The use of signal peptide domains as vaccine candidates

The use of signal peptide domains as vaccine candidates

A new era in anticancer peptide vaccines

CpG oligodeoxynucleotides augment antitumor efficacy of folate receptor α based DNA vaccine

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