Characterization of In Vitro Expanded Virus-Specific T cells for Adoptive Immunotherapy against Virus Infection

Ono, Tomotada; Fujita, Yuriko; Matano, Tetsuro; Takahashi, Satoshi; Morio, Tomohiro; Kawana-Tachikawa, Ai

doi:10.7883/yoken.jjid.2017.500

Cited by 1 publication

(1 citation statement)

References 28 publications

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“…Viral status was assayed using the PCR-rSSO (Polymerase chain reaction-reverse sequence specific oligonuclotide) HPV genotyping method (Luminex, Belgium). For immunological analyses, peripheral blood monocytes were cultured with HPV-16 E7 overlapping peptides for 2 weeks in the presence of interleukin-7 and -15 to expand HPV-16 E7–specific T cells ( 28 ). HPV-16 E7–specific IFN-γ producing cells in the expanded peripheral blood monocytes sampled preimmunization, and at weeks 16 and 24, were quantitated by enzyme-linked immunosorbent spot assay using HPV-16 E7 overlapping peptides as a stimulant.…”

Section: Methodsmentioning

confidence: 99%

Phase I and II randomized clinical trial of an oral therapeutic vaccine targeting human papillomavirus for treatment of cervical intraepithelial neoplasia 2 and 3

Kawana,

Kobayashi,

Ikeda

et al. 2023

JNCI Cancer Spectrum

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Background Although many human papillomavirus (HPV)–targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV-16 E7-expressing lacticaseibacillus-based oral vaccine. Methods In a double-blind, placebo-controlled, randomized trial, a total of 165 patients with HPV-16–positive high-grade cervical intraepithelial neoplasia 2 and 3 were assigned to orally administered placebo or low, intermediate, or high doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV-16 E7). In the 4 groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4, and 8 postenrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety. Results In per-protocol analyses, histopathological regression to normal (complete response) occurred in 13 (31.7%) of 41 high-dose recipients and in 5 (12.5%) of 40 placebo recipients (rate difference = 19.2, 95% confidence interval [CI] = 0.5 to 37.8). In patients positive for HPV-16 only, the clinical response rate was 40.0% (12 of 30) in high-dose recipients and 11.5% (3 of 26) in recipients of placebo (rate difference = 28.5, 95% CI = 4.3 to 50.0). There was no difference in adverse events that occurred in the high-dose and placebo groups (P = .83). The number of HPV-16 E7–specific interferon-γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P = .004). The regression to normal (complete response) rates among recipients with high levels of immune response were increased in a dose-dependent manner. Conclusion This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV-16–positive cervical intraepithelial neoplasia 2 and 3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show antineoplastic effects. Trial registration jRCT2031190034.

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Section: Methodsmentioning

confidence: 99%