Synthetic vaccine particles for durable cytolytic T lymphocyte responses and anti-tumor immunotherapy.
Synthetic vaccine particles for durable cytolytic T lymphocyte responses and anti-tumor immunotherapy.
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DOI：
10.1371/journal.pone.0197694
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Kishimoto TK
中科院分区：
文献类型：
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作者：
Ilyinskii PO;Kovalev GI;O'Neil CP;Roy CJ;Michaud AM;Drefs NM;Pechenkin MA;Fu FN;Johnston LPM;Ovchinnikov DA;Kishimoto TK
We previously reported that synthetic vaccine particles (SVP) encapsulating antigens and TLR agonists resulted in augmentation of immune responses with minimal production of systemic inflammatory cytokines. Here we evaluated two different polymer formulations of SVP-encapsulated antigens and tested their ability to induce cytolytic T lymphocytes (CTL) in combination with SVP-encapsulated adjuvants. One formulation led to efficient antigen processing and cross-presentation, rapid and sustained CTL activity, and expansion of CD8+ T cell effector memory cells locally and centrally, which persisted for at least 1–2 years after a single immunization. SVP therapeutic dosing resulted in suppression of tumor growth and a substantial delay in mortality in several syngeneic mouse cancer models. Treatment with checkpoint inhibitors and/or cytotoxic drugs, while suboptimal on their own, showed considerable synergy with SVP immunization. SVP encapsulation of endosomal TLR agonists provided superior CTL induction, therapeutic benefit and/or improved safety profile compared to free adjuvants. SVP vaccines encapsulating mutated HPV-16 E7 and E6/E7 recombinant proteins led to induction of broad CTL activity and strong inhibition of TC-1 tumor growth, even when administered therapeutically 13–14 days after tumor inoculation in animals bearing palpable tumors. A pilot study in non-human primates showed that SVP-encapsulated E7/E6 adjuvanted with SVP-encapsulated poly(I:C) led to robust induction of antigen-specific T and B cell responses.
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影响因子：
11.2
作者：
Chaoul, Nada;Fayolle, Catherine;Leclerc, Claude
通讯作者：
Leclerc, Claude
影响因子：
5.5
作者：
Ilyinskii, Petr O.;Roy, Christopher J.;O'Neil, Conlin P.;Browning, Erica A.;Pittet, Lynnelle A.;Altreuter, David H.;Alexis, Frank;Tonti, Elena;Shi, Jinjun;Basto, Pamela A.;Iannacone, Matteo;Radovic-Moreno, Aleksandar F.;Langer, Robert S.;Farokhzad, Omid C.;von Andrian, Ulrich H.;Johnston, Lloyd P. M.;Kishimoto, Takashi Kei
通讯作者：
Kishimoto, Takashi Kei
影响因子：
7.8
作者：
Gutjahr A;Phelip C;Coolen AL;Monge C;Boisgard AS;Paul S;Verrier B
通讯作者：
Verrier B
DOI：
10.1056/nejmoa1407222
发表时间：
2014-10-16
期刊：
The New England journal of medicine
影响因子：
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作者：
Maude SL;Frey N;Shaw PA;Aplenc R;Barrett DM;Bunin NJ;Chew A;Gonzalez VE;Zheng Z;Lacey SF;Mahnke YD;Melenhorst JJ;Rheingold SR;Shen A;Teachey DT;Levine BL;June CH;Porter DL;Grupp SA
通讯作者：
Grupp SA
影响因子：
8.8
作者：
通讯作者：
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