Journal Article
. 2019 Jun; 9(8):2299-2314.
doi: 10.7150/thno.30577.

Injectable polypeptide hydrogel-based co-delivery of vaccine and immune checkpoint inhibitors improves tumor immunotherapy

Huijuan Song 1 Pengxiang Yang 1 Pingsheng Huang 1 Chuangnian Zhang 1 Deling Kong 1 Weiwei Wang 1 
Affiliations
  • PMID: 31149045
  •     64 References
  •     21 citations

Abstract

Immunotherapy, an attractive option for cancer treatment, necessitates the direct stimulation of immune cells in vivo and the simultaneous effective inhibition of immunosuppressive tumor microenvironments. Methods: In the present study, we developed an injectable PEG-b-poly(L-alanine) hydrogel for co-delivery of a tumor vaccine and dual immune checkpoint inhibitors to increase tumor immunotherapy efficacy. Tumor cell lysates, granulocyte-macrophage colony stimulating factor (GM-CSF), and immune checkpoint inhibitors (anti-CTLA-4/PD-1 antibody) were readily encapsulated in the porous hydrogel during the spontaneous self-assembly of polypeptide in aqueous solution. Results: Sustained release of tumor antigens and GM-CSF persistently recruited and activated dendritic cells (DCs) and induced a strong T-cell response in vivo, which was further enhanced by the immune checkpoint therapy. The hydrogel vaccine also upregulated the production of IgG and the secretion of cytokines including IFN-γ, IL-4, and TNF-α. Importantly, the hydrogel-based combination therapy had superior immunotherapy effects against melanoma and 4T-1 tumor in comparison with the vaccine alone or in addition with a single immune checkpoint blockade. In studying the underlying mechanism, we found that the hydrogel-based combinatorial immunotherapy not only significantly increased the activated effector CD8+ T cells within the spleens and tumors of vaccinated mice, but also reduced the ratio of Tregs. Conclusion: Our findings indicate that the polypeptide hydrogel can be used as an effective sustained delivery platform for vaccines and immune checkpoint inhibitors, providing an advanced combinatorial immunotherapy approach for cancer treatment.

Keywords: Cancer immunotherapy; drug delivery.; hydrogel; immune checkpoint blockade; vaccine.

Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells.
Mark J Selby, John J Engelhardt, +4 authors, Alan J Korman.
Cancer Immunol Res, 2014 Apr 30; 1(1). PMID: 24777248
Highly Cited.
Nanoparticle-based immunotherapy for cancer.
Kun Shao, Santiswarup Singha, +3 authors, Pere Santamaria.
ACS Nano, 2014 Dec 04; 9(1). PMID: 25469470
Highly Cited. Review.
PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors.
Michael A Curran, Welby Montalvo, Hideo Yagita, James P Allison.
Proc Natl Acad Sci U S A, 2010 Feb 18; 107(9). PMID: 20160101    Free PMC article.
Highly Cited.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don't know.
Yufang Shi, Catherine H Liu, +9 authors, Satish Devadas.
Cell Res, 2006 Feb 14; 16(2). PMID: 16474424
Highly Cited. Review.
Anti-CTLA-4 therapy requires an Fc domain for efficacy.
Jessica R Ingram, Olga S Blomberg, +15 authors, Michael Dougan.
Proc Natl Acad Sci U S A, 2018 Mar 28; 115(15). PMID: 29581255    Free PMC article.
Highly Cited.
Biopolymers for Antitumor Implantable Drug Delivery Systems: Recent Advances and Future Outlook.
Sepehr Talebian, Javad Foroughi, +5 authors, Gordon G Wallace.
Adv Mater, 2018 May 15; 30(31). PMID: 29756237
Review.
Engineering Nanoparticles for Targeted Remodeling of the Tumor Microenvironment to Improve Cancer Immunotherapy.
Shan Gao, Dongjuan Yang, +6 authors, Kai Shi.
Theranostics, 2019 Jan 22; 9(1). PMID: 30662558    Free PMC article.
Highly Cited. Review.
Hydrogels and scaffolds for immunomodulation.
Ankur Singh, Nicholas A Peppas.
Adv Mater, 2014 Aug 27; 26(38). PMID: 25155610    Free PMC article.
Review.
Therapeutic cancer vaccines.
Fleur Pijpers, Richard Faint, Nish Saini.
Nat Rev Drug Discov, 2005 Aug 19; 4(8). PMID: 16106585
In situ thermal gelling polypeptide for chondrocytes 3D culture.
Bo Gyu Choi, Min Hee Park, +6 authors, Byeongmoon Jeong.
Biomaterials, 2010 Sep 25; 31(35). PMID: 20864172
Tailoring Biomaterials for Cancer Immunotherapy: Emerging Trends and Future Outlook.
Chao Wang, Yanqi Ye, +2 authors, Zhen Gu.
Adv Mater, 2017 May 31; 29(29). PMID: 28556553
Review.
Matrix-binding checkpoint immunotherapies enhance antitumor efficacy and reduce adverse events.
Jun Ishihara, Kazuto Fukunaga, +6 authors, Jeffrey A Hubbell.
Sci Transl Med, 2017 Nov 10; 9(415). PMID: 29118259
A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors.
Tingting Wang, Dangge Wang, +6 authors, Yaping Li.
Nat Commun, 2018 Apr 20; 9(1). PMID: 29670088    Free PMC article.
Personalized vaccines for cancer immunotherapy.
Ugur Sahin, Özlem Türeci.
Science, 2018 Mar 24; 359(6382). PMID: 29567706
Highly Cited. Review.
Towards personalized, tumour-specific, therapeutic vaccines for cancer.
Zhuting Hu, Patrick A Ott, Catherine J Wu.
Nat Rev Immunol, 2017 Dec 12; 18(3). PMID: 29226910    Free PMC article.
Highly Cited. Review.
Nano-, micro-, and macroscale drug delivery systems for cancer immunotherapy.
Pingsheng Huang, Xiaoli Wang, +4 authors, Weiwei Wang.
Acta Biomater, 2018 Dec 24; 85. PMID: 30579043
Review.
Self-assembled PEG-poly(l-valine) hydrogels as promising 3D cell culture scaffolds.
Huijuan Song, Guang Yang, +2 authors, Weiwei Wang.
J Mater Chem B, 2017 Mar 07; 5(9). PMID: 32263913
Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia.
Marco L Davila, Isabelle Riviere, +29 authors, Renier Brentjens.
Sci Transl Med, 2014 Feb 21; 6(224). PMID: 24553386    Free PMC article.
Highly Cited.
An immunogenic personal neoantigen vaccine for patients with melanoma.
Patrick A Ott, Zhuting Hu, +37 authors, Catherine J Wu.
Nature, 2017 Jul 06; 547(7662). PMID: 28678778    Free PMC article.
Highly Cited.
Cell therapy for skin wound using fibroblast encapsulated poly(ethylene glycol)-poly(L-alanine) thermogel.
Eun Jung Yun, Bora Yon, Min Kyung Joo, Byeongmoon Jeong.
Biomacromolecules, 2012 Mar 08; 13(4). PMID: 22394182
Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy.
Janis M Taube, Alison Klein, +7 authors, Robert A Anders.
Clin Cancer Res, 2014 Apr 10; 20(19). PMID: 24714771    Free PMC article.
Highly Cited.
Guanidinylated cationic nanoparticles as robust protein antigen delivery systems and adjuvants for promoting antigen-specific immune responses in vivo.
Pan Li, Gaona Shi, +7 authors, Deling Kong.
J Mater Chem B, 2016 Sep 07; 4(33). PMID: 32263357
In situ formed reactive oxygen species-responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy.
Chao Wang, Jinqiang Wang, +9 authors, Zhen Gu.
Sci Transl Med, 2018 Feb 23; 10(429). PMID: 29467299
Highly Cited.
Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer.
Ugur Sahin, Evelyna Derhovanessian, +47 authors, Özlem Türeci.
Nature, 2017 Jul 06; 547(7662). PMID: 28678784
Highly Cited.
Engineering biodegradable guanidyl-decorated PEG-PCL nanoparticles as robust exogenous activators of DCs and antigen cross-presentation.
Pan Li, Huijuan Song, +5 authors, Weiwei Wang.
Nanoscale, 2017 Sep 07; 9(36). PMID: 28876002
Granulocyte-macrophage colony-stimulating factor as a mediator of autoimmunity in multiple sclerosis.
Milos Kostic, Nikola Zivkovic, Ana Cvetanovic, Ivana Stojanovic.
J Neuroimmunol, 2018 Sep 11; 323. PMID: 30196820
Review.
Versatile biofunctionalization of polypeptide-based thermosensitive hydrogels via click chemistry.
Yilong Cheng, Chaoliang He, +4 authors, Xuesi Chen.
Biomacromolecules, 2013 Jan 15; 14(2). PMID: 23311471
Designing natural and synthetic immune tissues.
Emily A Gosselin, Haleigh B Eppler, Jonathan S Bromberg, Christopher M Jewell.
Nat Mater, 2018 May 23; 17(6). PMID: 29784994    Free PMC article.
Review.
PD-1 blockade induces responses by inhibiting adaptive immune resistance.
Paul C Tumeh, Christina L Harview, +23 authors, Antoni Ribas.
Nature, 2014 Nov 28; 515(7528). PMID: 25428505    Free PMC article.
Highly Cited.
Epitope-based vaccines: an update on epitope identification, vaccine design and delivery.
Alessandro Sette, John Fikes.
Curr Opin Immunol, 2003 Aug 06; 15(4). PMID: 12900280
Review.
A Powerful CD8+ T-Cell Stimulating D-Tetra-Peptide Hydrogel as a Very Promising Vaccine Adjuvant.
Zichao Luo, Qinjie Wu, +8 authors, Zhimou Yang.
Adv Mater, 2016 Nov 20; 29(5). PMID: 27859662
Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy.
Jason Park, Stephen H Wrzesinski, +12 authors, Tarek M Fahmy.
Nat Mater, 2012 Jul 17; 11(10). PMID: 22797827    Free PMC article.
Highly Cited.
Chemotherapeutic Delivery from a Self-Assembling Peptide Nanofiber Hydrogel for the Management of Glioblastoma.
Christina Karavasili, Emmanuel Panteris, +2 authors, Dimitrios G Fatouros.
Pharm Res, 2018 Jun 27; 35(8). PMID: 29943122
A self-assembling peptide acting as an immune adjuvant.
Jai S Rudra, Ye F Tian, Jangwook P Jung, Joel H Collier.
Proc Natl Acad Sci U S A, 2010 Jan 19; 107(2). PMID: 20080728    Free PMC article.
Highly Cited.
A facile approach to enhance antigen response for personalized cancer vaccination.
Aileen Weiwei Li, Miguel C Sobral, +10 authors, David J Mooney.
Nat Mater, 2018 Mar 07; 17(6). PMID: 29507416    Free PMC article.
Highly Cited.
Imageable antigen-presenting gold nanoparticle vaccines for effective cancer immunotherapy in vivo.
In-Hyun Lee, Ho-Keun Kwon, +7 authors, Sangyong Jon.
Angew Chem Int Ed Engl, 2012 Aug 01; 51(35). PMID: 22847719
Self-assembled PEG-b-PDPA-b-PGEM copolymer nanoparticles as protein antigen delivery vehicles to dendritic cells: preparation, characterization and cellular uptake.
Pan Li, Junhui Zhou, +4 authors, Deling Kong.
Regen Biomater, 2017 Feb 06; 4(1). PMID: 28149525    Free PMC article.
Injectable Bioresponsive Gel Depot for Enhanced Immune Checkpoint Blockade.
Shuangjiang Yu, Chao Wang, +9 authors, Zhen Gu.
Adv Mater, 2018 May 23; 30(28). PMID: 29786888
Extended release of perioperative immunotherapy prevents tumor recurrence and eliminates metastases.
Chun Gwon Park, Christina A Hartl, +3 authors, Michael S Goldberg.
Sci Transl Med, 2018 Mar 23; 10(433). PMID: 29563317
Highly Cited.
Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice.
Ying Wang, Lijing Su, +17 authors, Bruce Beutler.
Proc Natl Acad Sci U S A, 2018 Aug 29; 115(37). PMID: 30150374    Free PMC article.
Adoptive Cell Transfer: Is it a Promising Immunotherapy for Colorectal Cancer?
Jiaqiao Fan, Dong Shang, +3 authors, Jin-Ming Yang.
Theranostics, 2018 Dec 18; 8(20). PMID: 30555581    Free PMC article.
Review.
Switching the Immunogenicity of Peptide Assemblies Using Surface Properties.
Yi Wen, Amelia Waltman, Huifang Han, Joel H Collier.
ACS Nano, 2016 Sep 30; 10(10). PMID: 27680575    Free PMC article.
Infection-mimicking materials to program dendritic cells in situ.
Omar A Ali, Nathaniel Huebsch, +2 authors, David J Mooney.
Nat Mater, 2009 Jan 13; 8(2). PMID: 19136947    Free PMC article.
Highly Cited.
Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody.
Chao Wang, Yanqi Ye, +2 authors, Zhen Gu.
Nano Lett, 2016 Mar 22; 16(4). PMID: 26999507
Highly Cited.
Near-infrared labeled, ovalbumin loaded polymeric nanoparticles based on a hydrophilic polyester as model vaccine: In vivo tracking and evaluation of antigen-specific CD8(+) T cell immune response.
Sima Rahimian, Jan Willem Kleinovink, +9 authors, Wim E Hennink.
Biomaterials, 2014 Dec 03; 37. PMID: 25453974
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok.
N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431    Free PMC article.
Highly Cited.
A STING-activating nanovaccine for cancer immunotherapy.
Min Luo, Hua Wang, +13 authors, Jinming Gao.
Nat Nanotechnol, 2017 Apr 25; 12(7). PMID: 28436963    Free PMC article.
Highly Cited.
Engineering CAR-T cells: Design concepts.
Shivani Srivastava, Stanley R Riddell.
Trends Immunol, 2015 Jul 15; 36(8). PMID: 26169254    Free PMC article.
Highly Cited. Review.
Nivolumab plus ipilimumab in advanced melanoma.
Jedd D Wolchok, Harriet Kluger, +21 authors, Mario Sznol.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724867    Free PMC article.
Highly Cited.
Neoantigens in cancer immunotherapy.
Ton N Schumacher, Robert D Schreiber.
Science, 2015 Apr 04; 348(6230). PMID: 25838375
Highly Cited. Review.
Dual TLR agonist nanodiscs as a strong adjuvant system for vaccines and immunotherapy.
Rui Kuai, Xiaoqi Sun, +8 authors, James J Moon.
J Control Release, 2018 Apr 28; 282. PMID: 29702142    Free PMC article.
Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.
Brian T Fife, Kristen E Pauken, +6 authors, Jeffrey A Bluestone.
Nat Immunol, 2009 Sep 29; 10(11). PMID: 19783989    Free PMC article.
Highly Cited.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers.
Anu Sharma, Sumit K Subudhi, +6 authors, Padmanee Sharma.
Clin Cancer Res, 2018 Jul 29; 25(4). PMID: 30054281    Free PMC article.
Highly Cited.
Engineered Materials for Cancer Immunotherapy.
Alexander S Cheung, David J Mooney.
Nano Today, 2015 Dec 08; 10(4). PMID: 26640511    Free PMC article.
Engineering Dendritic-Cell-Based Vaccines and PD-1 Blockade in Self-Assembled Peptide Nanofibrous Hydrogel to Amplify Antitumor T-Cell Immunity.
Pengxiang Yang, Huijuan Song, +4 authors, Weiwei Wang.
Nano Lett, 2018 Jun 23; 18(7). PMID: 29932335
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Targeted antigen delivery to dendritic cell via functionalized alginate nanoparticles for cancer immunotherapy.
Chuangnian Zhang, Gaona Shi, +8 authors, Deling Kong.
J Control Release, 2017 Apr 18; 256. PMID: 28414151
Key roles of adjuvants in modern vaccines.
Steven G Reed, Mark T Orr, Christopher B Fox.
Nat Med, 2013 Dec 07; 19(12). PMID: 24309663
Highly Cited. Review.
Designer vaccine nanodiscs for personalized cancer immunotherapy.
Rui Kuai, Lukasz J Ochyl, +2 authors, James J Moon.
Nat Mater, 2016 Dec 27; 16(4). PMID: 28024156    Free PMC article.
Highly Cited.
The blockade of immune checkpoints in cancer immunotherapy.
Drew M Pardoll.
Nat Rev Cancer, 2012 Mar 23; 12(4). PMID: 22437870    Free PMC article.
Highly Cited. Review.
Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy.
Jaeyun Kim, Weiwei Aileen Li, +4 authors, David J Mooney.
Nat Biotechnol, 2014 Dec 09; 33(1). PMID: 25485616    Free PMC article.
Highly Cited.
TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy.
Christopher B Rodell, Sean P Arlauckas, +6 authors, Ralph Weissleder.
Nat Biomed Eng, 2019 Apr 25; 2(8). PMID: 31015631    Free PMC article.
Highly Cited.
Injectable polypeptide hydrogel for dual-delivery of antigen and TLR3 agonist to modulate dendritic cells in vivo and enhance potent cytotoxic T-lymphocyte response against melanoma.
Huijuan Song, Pingsheng Huang, +4 authors, Weiwei Wang.
Biomaterials, 2018 Jan 13; 159. PMID: 29324304
Regulatory circuits of T cell function in cancer.
Daniel E Speiser, Ping-Chih Ho, Grégory Verdeil.
Nat Rev Immunol, 2016 Aug 17; 16(10). PMID: 27526640
Highly Cited. Review.
Novel Delivery Systems for Checkpoint Inhibitors.
Purushottam Lamichhane, Rahul Deshmukh, +8 authors, Narottam Lamichhane.
Medicines (Basel), 2019 Aug 03; 6(3). PMID: 31373327    Free PMC article.
Review.
Peptide-based materials for cancer immunotherapy.
Lu Zhang, Yanyu Huang, +3 authors, Yuanpei Li.
Theranostics, 2019 Nov 07; 9(25). PMID: 31695802    Free PMC article.
Review.
Advances in Engineering Cells for Cancer Immunotherapy.
Xiao Xu, Teng Li, +4 authors, Ran Mo.
Theranostics, 2019 Nov 07; 9(25). PMID: 31695806    Free PMC article.
Review.
A supramolecular protein chaperone for vaccine delivery.
Zhongyan Wang, Yuna Shang, +6 authors, Jianfeng Liu.
Theranostics, 2020 Jan 07; 10(2). PMID: 31903143    Free PMC article.
Emerging Biomimetic Materials for Studying Tumor and Immune Cell Behavior.
Logan A Northcutt, Alejandra Suarez-Arnedo, Marjan Rafat.
Ann Biomed Eng, 2019 Oct 17; 48(7). PMID: 31617045    Free PMC article.
Review.
Injectable hydrogels for the sustained delivery of a HER2-targeted antibody for preventing local relapse of HER2+ breast cancer after breast-conserving surgery.
Xiaobin Chen, Maoli Wang, +4 authors, Jiandong Ding.
Theranostics, 2019 Sep 20; 9(21). PMID: 31534538    Free PMC article.
A Sacrificial PLA Block Mediated Route to Injectable and Degradable PNIPAAm-Based Hydrogels.
Vernon Tebong Mbah, Vincent Pertici, +4 authors, Thomas Trimaille.
Polymers (Basel), 2020 Apr 23; 12(4). PMID: 32316376    Free PMC article.
Advances in engineering local drug delivery systems for cancer immunotherapy.
Peter Abdou, Zejun Wang, +4 authors, Zhen Gu.
Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2020 Apr 08; 12(5). PMID: 32255276    Free PMC article.
Review.
Cell and tissue engineering in lymph nodes for cancer immunotherapy.
Alexander J Najibi, David J Mooney.
Adv Drug Deliv Rev, 2020 Aug 05; 161-162. PMID: 32750376    Free PMC article.
Systematic Review.
Encapsulation of LXR ligand by D-Nap-GFFY hydrogel enhances anti-tumorigenic actions of LXR and removes LXR-induced lipogenesis.
Ke Feng, Chuanrui Ma, +14 authors, Yajun Duan.
Theranostics, 2021 Jan 19; 11(6). PMID: 33456564    Free PMC article.
Immunostimulatory biomaterials to boost tumor immunogenicity.
Oluwaseyi T Shofolawe-Bakare, Larry D Stokes, +2 authors, Thomas A Werfel.
Biomater Sci, 2020 Oct 14; 8(20). PMID: 33049007    Free PMC article.
Review.
Recent strategies for nano-based PTT combined with immunotherapy: from a biomaterial point of view.
Xingyue Huang, Yang Lu, +2 authors, Ning Han.
Theranostics, 2021 Jun 24; 11(15). PMID: 34158866    Free PMC article.
Review.
Harnessing molecular recognition for localized drug delivery.
Renjie Liu, Ran Zuo, Gregory A Hudalla.
Adv Drug Deliv Rev, 2021 Jan 24; 170. PMID: 33484737    Free PMC article.
Review.
Production and Immunogenicity of a Tag-Free Recombinant Chimera Based on PfMSP-1 and PfMSP-3 Using Alhydrogel and Dipeptide-Based Hydrogels.
Gaurav Anand, Saikat Biswas, +2 authors, Virander Singh Chauhan.
Vaccines (Basel), 2021 Aug 07; 9(7). PMID: 34358198    Free PMC article.
Short Review on Advances in Hydrogel-Based Drug Delivery Strategies for Cancer Immunotherapy.
Hee Seung Seo, Chi-Pin James Wang, Wooram Park, Chun Gwon Park.
Tissue Eng Regen Med, 2021 Oct 02; 19(2). PMID: 34596839    Free PMC article.
Review.
Injectable biomaterials for treatment of glioblastoma.
Alexa R Anderson, Tatiana Segura.
Adv Mater Interfaces, 2021 Oct 19; 7(20). PMID: 34660174    Free PMC article.
Locally Injectable Hydrogels for Tumor Immunotherapy.
Xinyi Zhang, Xiaonan Guo, Yan Wu, Jie Gao.
Gels, 2021 Nov 30; 7(4). PMID: 34842684    Free PMC article.
Review.
Emerging biomaterial-based strategies for personalized therapeutic in situ cancer vaccines.
Dixita Ishani Viswanath, Hsuan-Chen Liu, +2 authors, Alessandro Grattoni.
Biomaterials, 2021 Dec 14; 280. PMID: 34902729    Free PMC article.
Review.
Injectable Hydrogel as a Unique Platform for Antitumor Therapy Targeting Immunosuppressive Tumor Microenvironment.
Yushuai Liu, Yuanyuan Geng, +3 authors, Honglin Jin.
Front Immunol, 2022 Feb 04; 12. PMID: 35111169    Free PMC article.
Review.
3D-Printable Oxygen- and Drug-Carrying Nanocomposite Hydrogels for Enhanced Cell Viability.
Ravi Kumar, Nermin Seda Kehr.
Nanomaterials (Basel), 2022 Apr 24; 12(8). PMID: 35458012    Free PMC article.
Development of cancer immunotherapy based on PD-1/PD-L1 pathway blockade.
Min Zhang, Kehai Liu, Mingfu Wang.
RSC Adv, 2019 Oct 22; 9(58). PMID: 35528929    Free PMC article.
Review.