HER2-Specific T-Cell Immune Responses in Patients Vaccinated with Truncated HER2 Protein Complexed with Nanogels of Cholesteryl Pullulan

Kitano, Shigehisa; Kageyama, Shinichi; Nagata, Yasunobu; Miyahara, Yoshihiro; Hiasa, Atsunori; Naota, Hiroaki; Okumura, Satoshi; Imai, Hiroshi; Shiraishi, Taizo; Masuya, Masahiro; Nishikawa, Masakatsu; Sunamoto, Junzo; Akiyoshi, Kazunari; Kanematsu, Takashi; Scott, Andrew M.; Murphy, Roger; Hoffman, Eric W.; Old, Lloyd J.; Shiku, Hiroshi

doi:10.1158/1078-0432.ccr-06-1546

Cited by 114 publications

(79 citation statements)

References 19 publications

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“…Although there are only very limited data on the effect of multiple cycles of vaccination in humans, a few studies support the idea of progressive strengthening of tumor-specific immunity over prolonged courses of vaccination (18,20,44). As we observed in this study with broadening of immune responses upon repeated vaccination, the application of serial vaccinations might indeed improve the immunological, and hopefully also clinical, efficacy of cancer vaccines.…”

Section: Discussionsupporting

confidence: 59%

“…We also detected MAGE-A3-specific CD8 ϩ T cell responses in patients who developed the highest-titered broadly specific antibody responses after vaccination. So far, few trials have been conducted in which recombinant proteins were used as immunogen in cancer vaccines (12)(13)(14)(15)(16), and if T cell responses have been reported, they consisted mainly of CD4 ϩ T cells (17,18). Two reports have shown that vaccination with CT antigen NY-ESO-1 as a recombinant protein, formulated either with saponin-based adjuvant ISCOMATRIX or with cholesterol-bearing hydrophobized pullulan, induced strong antibody as well as CD4 ϩ and CD8 ϩ responses in the majority of patients (19,20).…”

Section: Discussionmentioning

confidence: 99%

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Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming

Atanackovic

Altorki

Cao

et al. 2008

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

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144

107

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We previously reported results of a phase II trial in which recombinant MAGE-A3 protein was administered with or without adjuvant AS02B to 18 non-small-cell lung cancer (NSCLC) patients after tumor resection. We found that the presence of adjuvant was essential for the development of humoral and cellular responses against selected MAGE-A3 epitopes. In our current study, 14 patients that still had no evidence of disease up to 3 years after vaccination with MAGE-A3 protein with or without adjuvant received an additional four doses of MAGE-A3 protein with adjuvant AS02B. After just one boost injection, six of seven patients originally vaccinated with MAGE-A3 protein plus adjuvant reached again their peak antibody titers against MAGE-A3 attained during the first vaccination. All seven patients subsequently developed even stronger antibody responses. Furthermore, booster vaccination widened the spectrum of CD4 ϩ and CD8 ؉ T cells against various new and known MAGE-A3 epitopes. In contrast, only two of seven patients originally vaccinated with MAGE-A3 protein alone developed high-titer antibodies to MAGE-A3, and all these patients showed very limited CD4 ؉ and no CD8 ؉ T cell reactivity, despite now receiving antigen in the presence of adjuvant. Our results underscore the importance of appropriate antigen priming using an adjuvant for generating persistent B and T cell memory and allowing typical booster responses with reimmunization. In contrast, absence of adjuvant at priming compromises further immunization attempts. These data provide an immunological rationale for vaccine design in light of recently reported favorable clinical responses in NSCLC patients after vaccination with MAGE-A3 protein plus adjuvant AS02B.antibody ͉ CD4 ϩ T cell ͉ CD8 ϩ T cell ͉ immunization ͉ non-small-cell lung cancer

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming

Atanackovic

Altorki

Cao

et al. 2008

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

Self Cite

144

107

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show abstract

“…[25][26][27][28] A number of methods for targeting antigens to LN macrophages have been investigated as part of the ongoing development of lymphatic-targeted vaccines. It was reported that cholesteryl pullulan (CHP) nanogels induce tumor regression in some patients with malignant tumors, 29,30 and CD169-positive macrophages in LN sinus captured CHP nanogels and worked as APCs. 31 Thus, lymphatic-targeting materials might be a promising approach to improving vaccine efficacy, and CD169-positive macrophages are now of interest as APCs to which antigens might be efficiently delivered.…”

Section: Discussionmentioning

confidence: 99%

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

Fujiwara

Saito

Shiota

et al. 2018

JCEH

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“…12,13 Both CD4 and CD8 T cells are efficiently activated by DCs pulsed with a complex of CHP and NY-ESO-1 protein (CHP-NY-ESO-1) in vitro.…”

mentioning

confidence: 99%

A phase I study of vaccination with NY‐ESO‐1f peptide mixed with Picibanil OK‐432 and Montanide ISA‐51 in patients with cancers expressing the NY‐ESO‐1 antigen

Kakimi

Isobe

Uenaka

et al. 2011

Intl Journal of Cancer

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We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 lg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients.The NY-ESO-1 antigen was originally identified in esophageal cancer by serological expression cloning (SEREX) using autologous patient serum.1,2 NY-ESO-1 expression is observed in a wide range of human malignancies, 3,4 but the expression is restricted to germ cells in the testes in normal adult tissues. 1,3Therefore, NY-ESO-1 has emerged as a prototype of a class of cancer/testis (CT) antigens. 5More than 100 patients with NY-ESO-1-expressing tumors have received the NY-ESO-1 vaccine either as fulllength recombinant protein given as protein alone, with ISCOMATRIX V R or cholesterol-bearing hydrophobized pullulan (CHP), delivered in a recombinant vaccinia or fowlpox vector, or as the NY-ESO-1b peptide given with various adjuvants. [6][7][8][9][10][11] These studies established safety with various preparations of the NY-ESO-1 vaccine, showing toxicity to be limited to Grade 1 or 2 injection-site reactions or flu-like

show abstract

HER2-Specific T-Cell Immune Responses in Patients Vaccinated with Truncated HER2 Protein Complexed with Nanogels of Cholesteryl Pullulan

Cited by 114 publications

References 19 publications

Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming

Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

A phase I study of vaccination with NY‐ESO‐1f peptide mixed with Picibanil OK‐432 and Montanide ISA‐51 in patients with cancers expressing the NY‐ESO‐1 antigen

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