Journal Article
. 2015 Dec; 4(2):95-100.
doi: 10.1158/2326-6066.CIR-14-0126.

Vaccines Combined with Immune Checkpoint Antibodies Promote Cytotoxic T-cell Activity and Tumor Eradication

Omar A Ali 1 Sarah A Lewin 2 Glenn Dranoff 3 David J Mooney 4 
  • PMID: 26669718
  •     14 References
  •     64 citations


We demonstrate that a poly(lactide-co-glycolide) (PLG) cancer vaccine can be used in combination with immune checkpoint antibodies, anti-CTLA-4 or anti-PD-1, to enhance cytotoxic T-cell (CTL) activity and induce the regression of solid B16 tumors in mice. Combination therapy obviated the need for vaccine boosting and significantly skewed intratumoral reactions toward CTL activity, resulting in the regression of B16 tumors up to 50 mm(2) in size and 75% survival rates. These data suggest that combining material-based cancer vaccines with checkpoint antibodies has the potential to mediate tumor regression in humans.

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.
Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
Philip W Kantoff, Celestia S Higano, +11 authors, IMPACT Study Investigators.
N Engl J Med, 2010 Sep 08; 363(5). PMID: 20818862
Highly Cited.
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
In situ regulation of DC subsets and T cells mediates tumor regression in mice.
Omar A Ali, Dwaine Emerich, Glenn Dranoff, David J Mooney.
Sci Transl Med, 2010 Apr 07; 1(8). PMID: 20368186    Free PMC article.
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.
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies.
Karl S Peggs, Sergio A Quezada, +2 authors, James P Allison.
J Exp Med, 2009 Jul 08; 206(8). PMID: 19581407    Free PMC article.
Highly Cited.
Immune therapy for cancer.
Michael Dougan, Glenn Dranoff.
Annu Rev Immunol, 2008 Nov 15; 27. PMID: 19007331
Highly Cited. Review.
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.
Checkpoint blockade in cancer immunotherapy.
Alan J Korman, Karl S Peggs, James P Allison.
Adv Immunol, 2006 May 30; 90. PMID: 16730267    Free PMC article.
Highly Cited. Review.
PD-1 targeting in cancer immunotherapy.
Robert Ferris.
Cancer, 2012 Oct 09; 119(23). PMID: 23042635    Free PMC article.
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.
Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma.
Jedd D Wolchok, F Stephen Hodi, +9 authors, Alan J Korman.
Ann N Y Acad Sci, 2013 Jun 19; 1291. PMID: 23772560    Free PMC article.
Highly Cited. Review.
Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors.
Jaikumar Duraiswamy, Karen M Kaluza, Gordon J Freeman, George Coukos.
Cancer Res, 2013 May 02; 73(12). PMID: 23633484    Free PMC article.
Highly Cited.
Identification of immune factors regulating antitumor immunity using polymeric vaccines with multiple adjuvants.
Omar A Ali, Catia Verbeke, +6 authors, David J Mooney.
Cancer Res, 2014 Feb 01; 74(6). PMID: 24480625    Free PMC article.
Prognostic Role of Programmed Death Ligand-1 Expression in Breast Cancer: A Systematic Review and Meta-Analysis.
Xue Li, Minghuan Li, +4 authors, Jinming Yu.
Target Oncol, 2016 Jul 17; 11(6). PMID: 27422273
Systematic Review.
Effect of HSV-IL12 Loaded Tumor Cell-Based Vaccination in a Mouse Model of High-Grade Neuroblastoma.
David F Bauer, Larisa Pereboeva, +5 authors, Lawrence S Lamb.
J Immunol Res, 2016 Sep 10; 2016. PMID: 27610392    Free PMC article.
Fusion of the dendritic cell-targeting chemokine MIP3α to melanoma antigen Gp100 in a therapeutic DNA vaccine significantly enhances immunogenicity and survival in a mouse melanoma model.
James T Gordy, Kun Luo, +2 authors, Richard B Markham.
J Immunother Cancer, 2016 Dec 27; 4. PMID: 28018602    Free PMC article.
Inhibitory Receptors Induced by VSV Viroimmunotherapy Are Not Necessarily Targets for Improving Treatment Efficacy.
Kevin G Shim, Shane Zaidi, +8 authors, Richard G Vile.
Mol Ther, 2017 Feb 27; 25(4). PMID: 28237836    Free PMC article.
Prospect of Immunotherapy for Glioblastoma: Tumor Vaccine, Immune Checkpoint Inhibitors and Combination Therapy.
Eiichi Ishikawa, Tetsuya Yamamoto, Akira Matsumura.
Neurol Med Chir (Tokyo), 2017 May 26; 57(7). PMID: 28539528    Free PMC article.
Combination therapy of cancer with cancer vaccine and immune checkpoint inhibitors: A mathematical model.
Xiulan Lai, Avner Friedman.
PLoS One, 2017 May 26; 12(5). PMID: 28542574    Free PMC article.
Combination therapy for melanoma with BRAF/MEK inhibitor and immune checkpoint inhibitor: a mathematical model.
Xiulan Lai, Avner Friedman.
BMC Syst Biol, 2017 Jul 21; 11(1). PMID: 28724377    Free PMC article.
Synthetic immune niches for cancer immunotherapy.
Jorieke Weiden, Jurjen Tel, Carl G Figdor.
Nat Rev Immunol, 2017 Aug 31; 18(3). PMID: 28853444
miR-125b-1 and miR-378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.
Hironori Tanaka, Shoichi Hazama, +24 authors, Hiroaki Nagano.
Cancer Sci, 2017 Sep 01; 108(11). PMID: 28859241    Free PMC article.
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.
Synergy of Immune Checkpoint Blockade with a Novel Synthetic Consensus DNA Vaccine Targeting TERT.
Elizabeth K Duperret, Megan C Wise, +8 authors, David B Weiner.
Mol Ther, 2017 Dec 19; 26(2). PMID: 29249395    Free PMC article.
Langerhans-type dendritic cells electroporated with TRP-2 mRNA stimulate cellular immunity against melanoma: Results of a phase I vaccine trial.
David J Chung, Richard D Carvajal, +8 authors, James W Young.
Oncoimmunology, 2018 Jan 04; 7(1). PMID: 29296525    Free PMC article.
Vaccination with autologous myeloblasts admixed with GM-K562 cells in patients with advanced MDS or AML after allogeneic HSCT.
Vincent T Ho, Haesook T Kim, +13 authors, Robert J Soiffer.
Blood Adv, 2018 Jan 04; 1(24). PMID: 29296875    Free PMC article.
Anti-IL-10-mediated Enhancement of Antitumor Efficacy of a Dendritic Cell-targeting MIP3α-gp100 Vaccine in the B16F10 Mouse Melanoma Model Is Dependent on Type I Interferons.
James T Gordy, Kun Luo, +2 authors, Richard B Markham.
J Immunother, 2018 Jan 16; 41(4). PMID: 29334492    Free PMC article.
Cancer vaccine: learning lessons from immune checkpoint inhibitors.
ZhenLong Ye, Qiming Qian, HuaJun Jin, QiJun Qian.
J Cancer, 2018 Jan 19; 9(2). PMID: 29344272    Free PMC article.
Inhibition of tumor growth by cancer vaccine combined with metronomic chemotherapy and anti-PD-1 in a pre-clinical setting.
Annacarmen Petrizzo, Angela Mauriello, +11 authors, Luigi Buonaguro.
Oncotarget, 2018 Feb 10; 9(3). PMID: 29423067    Free PMC article.
Induction of necrotic cell death and activation of STING in the tumor microenvironment via cationic silica nanoparticles leading to enhanced antitumor immunity.
Myunggi An, Chunsong Yu, +4 authors, Haipeng Liu.
Nanoscale, 2018 May 09; 10(19). PMID: 29737353    Free PMC article.
Optimized dendritic cell vaccination induces potent CD8 T cell responses and anti-tumor effects in transgenic mouse melanoma models.
Mareike Grees, Adi Sharbi-Yunger, +8 authors, Viktor Umansky.
Oncoimmunology, 2018 Jun 15; 7(7). PMID: 29900058    Free PMC article.
Survival analysis of multiple peptide vaccination for the selection of correlated peptides in urological cancers.
Masanori Noguchi, Noriko Koga, +6 authors, Kyogo Itoh.
Cancer Sci, 2018 Jun 26; 109(9). PMID: 29938870    Free PMC article.
Cancer Stem Cell Vaccination With PD-L1 and CTLA-4 Blockades Enhances the Eradication of Melanoma Stem Cells in a Mouse Tumor Model.
Fang Zheng, Jianzhong Dang, +7 authors, Qiao Li.
J Immunother, 2018 Aug 01; 41(8). PMID: 30063587    Free PMC article.
Identification of a novel HLA-A24-restricted cytotoxic T lymphocyte epitope peptide derived from mesothelin in pancreatic cancer.
Mariko Tsukagoshi, Satoshi Wada, +6 authors, Hiroki Yamaue.
Oncotarget, 2018 Aug 25; 9(59). PMID: 30140382    Free PMC article.
Immuno-Oncology: Emerging Targets and Combination Therapies.
Henry T Marshall, Mustafa B A Djamgoz.
Front Oncol, 2018 Sep 08; 8. PMID: 30191140    Free PMC article.
Highly Cited. Review.
Potentiating cancer vaccine efficacy in liver cancer.
Maria Tagliamonte, Annacarmen Petrizzo, +3 authors, Luigi Buonaguro.
Oncoimmunology, 2018 Oct 06; 7(10). PMID: 30288355    Free PMC article.
Protein-based nanoparticles in cancer vaccine development.
Medea Neek, Tae Il Kim, Szu-Wen Wang.
Nanomedicine, 2018 Oct 07; 15(1). PMID: 30291897    Free PMC article.
Safety and Efficacy of Therapeutic Cancer Vaccines Alone or in Combination With Immune Checkpoint Inhibitors in Cancer Treatment.
Jing Zhao, Ye Chen, Zhen-Yu Ding, Ji-Yan Liu.
Front Pharmacol, 2019 Nov 05; 10. PMID: 31680963    Free PMC article.
Evaluation of a ConvitVax/anti-PD-1 combined immunotherapy for breast cancer treatment.
María José Godoy-Calderón, Eglys González-Marcano, Jeismar Carballo, Ana Federica Convit.
Oncotarget, 2019 Nov 26; 10(61). PMID: 31762937    Free PMC article.
Precision health for breast cancer metastasis: biomaterial scaffolds as an engineered metastatic niche to define, study, and monitor metastatic progression.
Grace G Bushnell, Max S Wicha, Jacqueline S Jeruss, Lonnie D Shea.
Oncoscience, 2020 Jan 28; 6(11-12). PMID: 31984215    Free PMC article.
Biohybrid Vaccines for Improved Treatment of Aggressive Melanoma with Checkpoint Inhibitor.
Flavia Fontana, Manlio Fusciello, +9 authors, Hélder A Santos.
ACS Nano, 2019 May 18; 13(6). PMID: 31100004    Free PMC article.
Advances in immunotherapy delivery from implantable and injectable biomaterials.
David G Leach, Simon Young, Jeffrey D Hartgerink.
Acta Biomater, 2019 Feb 17; 88. PMID: 30771535    Free PMC article.
Novel approaches for the design, delivery and administration of vaccine technologies.
J Wallis, D P Shenton, R C Carlisle.
Clin Exp Immunol, 2019 Apr 10; 196(2). PMID: 30963549    Free PMC article.
Intradermal DNA vaccination combined with dual CTLA-4 and PD-1 blockade provides robust tumor immunity in murine melanoma.
Spela Kos, Alessandra Lopes, +6 authors, Gaelle Vandermeulen.
PLoS One, 2019 Jun 01; 14(5). PMID: 31150505    Free PMC article.
Neoantigen vaccine: an emerging tumor immunotherapy.
Miao Peng, Yongzhen Mo, +10 authors, Zhaoyang Zeng.
Mol Cancer, 2019 Aug 25; 18(1). PMID: 31443694    Free PMC article.
Highly Cited. Review.
Enhanced anti-tumor immunotherapy by dissolving microneedle patch loaded ovalbumin.
Sung-Ju Lee, Hyeon-Seong Lee, +8 authors, Sung-Tae Yee.
PLoS One, 2019 Aug 07; 14(8). PMID: 31386690    Free PMC article.
Novel Vaccine Targeting Colonic Adenoma: a Pre-clinical Model.
Toan Pham, Sandra Carpinteri, +7 authors, Robert G Ramsay.
J Gastrointest Surg, 2019 Jan 10; 23(3). PMID: 30623377
Biomaterial-based platforms for in situ dendritic cell programming and their use in antitumor immunotherapy.
João Calmeiro, Mylène Carrascal, +3 authors, Bruno Miguel Neves.
J Immunother Cancer, 2019 Sep 06; 7(1). PMID: 31484548    Free PMC article.
Remarkable antitumor effect of nivolumab in a patient with metastatic renal cell carcinoma previously treated with a peptide-based vaccine.
Ryoma Kurahashi, Takanobu Motoshima, +8 authors, Tomomi Kamba.
IJU Case Rep, 2020 Aug 04; 3(2). PMID: 32743467    Free PMC article.
Combinatorial Immunotherapies for Metastatic Colorectal Cancer.
Eline Janssen, Beatriz Subtil, +2 authors, Daniele V F Tauriello.
Cancers (Basel), 2020 Jul 16; 12(7). PMID: 32664619    Free PMC article.
Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells.
Fei-Long Qi, Mei-Fang Wang, +3 authors, Su-Ping Li.
Acta Pharmacol Sin, 2020 May 30; 41(7). PMID: 32467568    Free PMC article.
Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.
Erika J Crosby, Chaitanya R Acharya, +23 authors, Zachary C Hartman.
Clin Cancer Res, 2020 Aug 01; 26(17). PMID: 32732224    Free PMC article.
Turning the corner on therapeutic cancer vaccines.
Robert E Hollingsworth, Kathrin Jansen.
NPJ Vaccines, 2019 Feb 19; 4. PMID: 30774998    Free PMC article.
Highly Cited. Review.
An effective peptide vaccine strategy circumventing clonal MHC heterogeneity of murine myeloid leukaemia.
A-Ri Shin, Sang-Eun Lee, +3 authors, Tai-Gyu Kim.
Br J Cancer, 2020 Jul 01; 123(6). PMID: 32595211    Free PMC article.
Innate Immune Modulation by GM-CSF and IL-3 in Health and Disease.
Francesco Borriello, Maria Rosaria Galdiero, +3 authors, Gianni Marone.
Int J Mol Sci, 2019 Feb 17; 20(4). PMID: 30769926    Free PMC article.
T lymphocytes in hepatocellular carcinoma immune microenvironment: insights into human immunology and immunotherapy.
Jin Bian, Jianzhen Lin, +5 authors, Haitao Zhao.
Am J Cancer Res, 2021 Jan 09; 10(12). PMID: 33415021    Free PMC article.
Use of plasma ctDNA as a potential biomarker for longitudinal monitoring of a patient with metastatic high-risk upper tract urothelial carcinoma receiving pembrolizumab and personalized neoepitope-derived multipeptide vaccinations: a case report.
Carolin Blumendeller, Julius Boehme, +12 authors, Saskia Biskup.
J Immunother Cancer, 2021 Jan 13; 9(1). PMID: 33431630    Free PMC article.
Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8+ T Cell Responses via CD169+ Macrophages and cDC1.
Joanna Grabowska, Dorian A Stolk, +6 authors, Joke M M den Haan.
Vaccines (Basel), 2021 Jan 21; 9(1). PMID: 33467048    Free PMC article.
Vaccine Therapies for Cancer: Then and Now.
Michael A Morse, William R Gwin, Duane A Mitchell.
Target Oncol, 2021 Jan 30; 16(2). PMID: 33512679    Free PMC article.
Fundamentals of Cancer Immunology and Their Application to Cancer Vaccines.
Timothy N J Bullock.
Clin Transl Sci, 2020 Aug 10; 14(1). PMID: 32770735    Free PMC article.
Vaccine Increases the Diversity and Activation of Intratumoral T Cells in the Context of Combination Immunotherapy.
Lucas A Horn, Kristen Fousek, +5 authors, Claudia Palena.
Cancers (Basel), 2021 Mar 07; 13(5). PMID: 33669155    Free PMC article.
The Peptide Vaccine of the Future.
Annika Nelde, Hans-Georg Rammensee, Juliane S Walz.
Mol Cell Proteomics, 2021 Feb 16; 20. PMID: 33583769    Free PMC article.
Cancer Vaccines, Adjuvants, and Delivery Systems.
Samantha J Paston, Victoria A Brentville, Peter Symonds, Lindy G Durrant.
Front Immunol, 2021 Apr 17; 12. PMID: 33859638    Free PMC article.
Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines.
Lu Han, Ke Peng, +4 authors, Zhi-Xiang Yuan.
Front Pharmacol, 2021 May 28; 12. PMID: 34040536    Free PMC article.
Delivering Two Tumour Antigens Survivin and Mucin-1 on Virus-Like Particles Enhances Anti-Tumour Immune Responses.
Katrin Campbell, Vivienne L Young, +5 authors, Sarah L Young.
Vaccines (Basel), 2021 Jun 03; 9(5). PMID: 34066318    Free PMC article.
An Antigen-Delivery Protein Nanoparticle Combined with Anti-PD-1 Checkpoint Inhibitor Has Curative Efficacy in an Aggressive Melanoma Model.
Medea Neek, Jo Anne Tucker, +2 authors, Szu-Wen Wang.
Adv Ther (Weinh), 2021 Jun 19; 3(12). PMID: 34141865    Free PMC article.
Combining vaccines and immune checkpoint inhibitors to prime, expand, and facilitate effective tumor immunotherapy.
Julie M Collins, Jason M Redman, James L Gulley.
Expert Rev Vaccines, 2018 Jul 31; 17(8). PMID: 30058393    Free PMC article.
Characterization of neoantigen-specific T cells in cancer resistant to immune checkpoint therapies.
Shamin Li, Yannick Simoni, +10 authors, Evan W Newell.
Proc Natl Acad Sci U S A, 2021 Jul 22; 118(30). PMID: 34285073    Free PMC article.
The Clinical Application of Neoantigens in Esophageal Cancer.
Yi-Min Gu, Yue Zhuo, Long-Qi Chen, Yong Yuan.
Front Oncol, 2021 Aug 14; 11. PMID: 34386424    Free PMC article.
Translational Applications of Hydrogels.
Santiago Correa, Abigail K Grosskopf, +4 authors, Eric A Appel.
Chem Rev, 2021 May 04; 121(18). PMID: 33938724    Free PMC article.
Engineered biomaterials for cancer immunotherapy.
Lulu Cai, Jialu Xu, +4 authors, Kam W Leong.
MedComm (2020), 2020 May 27; 1(1). PMID: 34766108    Free PMC article.
Selective IL-1 activity on CD8+ T cells empowers antitumor immunity and synergizes with neovasculature-targeted TNF for full tumor eradication.
Bram Van Den Eeckhout, Leander Huyghe, +8 authors, Jan Tavernier.
J Immunother Cancer, 2021 Nov 14; 9(11). PMID: 34772757    Free PMC article.
Potential Applications of Microparticulate-Based Bacterial Outer Membrane Vesicles (OMVs) Vaccine Platform for Sexually Transmitted Diseases (STDs): Gonorrhea, Chlamydia, and Syphilis.
Christiane Chbib, Sarthak M Shah, Rikhav P Gala, Mohammad N Uddin.
Vaccines (Basel), 2021 Nov 28; 9(11). PMID: 34835176    Free PMC article.
Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier.
Somayeh Vafaei, Angelina O Zekiy, +4 authors, Majid Zamani.
Cancer Cell Int, 2022 Jan 05; 22(1). PMID: 34980128    Free PMC article.
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.
Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma.
Sofie Kirial Mørk, Mohammad Kadivar, +17 authors, Inge Marie Svane.
Oncoimmunology, 2022 Jan 18; 11(1). PMID: 35036074    Free PMC article.
Therapeutic strategies to remodel immunologically cold tumors.
Minyu Wang, Sen Wang, +2 authors, Paul J Neeson.
Clin Transl Immunology, 2020 Dec 08; 9(12). PMID: 35136604    Free PMC article.