Chitosan–PEGHuman PBMCNoneYesIn vitro glioblastoma cells9898. C.-T. Tsao, F. M. Kievit, A. Ravanpay, A. E. Erickson, M. C. Jensen, R. G. Ellenbogen et al., “ Thermoreversible poly(ethylene glycol)-g-chitosan hydrogel as a therapeutic T lymphocyte depot for localized glioblastoma immunotherapy,” Biomacromolecules 15(7), 2656–2662 (2014). https://doi.org/10.1021/bm500502nChitosan–PEGHuman CAR-T cellsSelf-expression of IL-15YesHuman retinoblastoma9999. K. Wang, Y. Chen, S. Ahn, M. Zheng, E. Landoni, G. Dotti et al., “ GD2-specific CAR T cells encapsulated in an injectable hydrogel control retinoblastoma and preserve vision,” Nat. Cancer 1(10), 990–997 (2020). https://doi.org/10.1038/s43018-020-00119-yElimination of tumors and 100% survival with gel-delivered IL-15 CARPCL–PEG–PPG copolymerHuman CD4+ T cellsNoneYesHuman CD4+ T cell survival over 5 days100100. K. Brewer, B. Gundsambuu, P. Facal Marina, S. C. Barry, and A. Blencowe, “ Thermoresponsive poly(ε-caprolactone)-poly(ethylene/propylene glycol) copolymers as injectable hydrogels for cell therapies,” Polymers 12(2), 367 (2020). https://doi.org/10.3390/polym12020367PEG–heparinHuman CD4+ T cellsCCL21YesIncreased human CD4+ T cell proliferation101101. E. Pérez del Río, F. Santos, X. Rodriguez Rodriguez, M. Martínez-Miguel, R. Roca-Pinilla, A. Arís et al., “ CCL21-loaded 3D hydrogels for T cell expansion and differentiation,” Biomaterials 259, 120313 (2020). https://doi.org/10.1016/j.biomaterials.2020.120313PEGHuman CD3+ T cellsNoneYesProliferation upon restimulation of escaped T cells102102. J. Yan, B. Gundsambuu, M. Krasowska, K. Platts, P. Facal Marina, C. Gerber et al., “ Injectable Diels–Alder cycloaddition hydrogels with tuneable gelation, stiffness and degradation for the sustained release of T-lymphocytes,” J. Mater. Chem. B. 10, 3329 (2022). https://doi.org/10.1039/D2TB00274DChitosanHuman PBMC and TILNoneYesIn vitro renal cancer, breast cancer and melanoma103103. A. Monette, C. Ceccaldi, E. Assaad, S. Lerouge, and R. Lapointe, “ Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies,” Biomaterials 75, 237–249 (2016). https://doi.org/10.1016/j.biomaterials.2015.10.021Polyisocyanopeptide (PIC) + GRGDS peptideHuman T cells, DC and NK, mouse T cellsNoneYesMigration in mice in vivo without tumors104104. J. Weiden, D. Voerman, Y. Dölen, R. K. Das, A. van Duffelen, R. Hammink et al., “ Injectable biomimetic hydrogels as tools for efficient T cell expansion and delivery,” Front. Immunol. 9, 2798 (2018). https://doi.org/10.3389/fimmu.2018.02798Hyaluronic acidHuman CAR-T cellsNoneYesIn vitro glioma cell line105105. A. F. Atik, C. M. Suryadevara, R. M. Schweller, J. L. West, P. Healy, J. E. Herndon Ii et al., “ Hyaluronic acid based low viscosity hydrogel as a novel carrier for convection enhanced delivery of CAR T cells,” J. Clin. Neurosci. 56, 163–168 (2018). https://doi.org/10.1016/j.jocn.2018.06.005Alginate + GFOGER collagen-like peptideHuman CAR-T cellsIL-15 agonist, CD137, CD28, CD3NoMouse breast cancer resection model106106. S. B. Stephan, A. M. Taber, I. Jileaeva, E. P. Pegues, C. L. Sentman, and M. T. Stephan, “ Biopolymer implants enhance the efficacy of adoptive T cell therapy,” Nat. Biotechnol. 33(1), 97–101 (2015). https://doi.org/10.1038/nbt.3104Regression in 60% of treated mice vs 0% survival in untreated miceAlginate + GFOGER collagen-like peptideHuman CAR-T cellsIL-15 agonist, CD137, CD28, CD3, STING agonistNoMouse pancreatic cancer and melanoma models107107. T. T. Smith, H. F. Moffett, S. B. Stephan, C. F. Opel, A. G. Dumigan, X. Jiang et al., “ Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors,” J. Clin. Invest. 127(6), 2176–2191 (2017). https://doi.org/10.1172/JCI87624Complete pancreatic tumor elimination in 40% of treated mice, with persistent immunity on tumor rechallenge.Fibrin-coated NitinolHuman CAR-T cellsIL-15 agonist, CD137, CD28, CD3NoMouse ovarian cancer model108108. M. E. Coon, S. B. Stephan, V. Gupta, C. P. Kealey, and M. T. Stephan, “ Nitinol thin films functionalized with CAR-T cells for the treatment of solid tumours,” Nat. Biomed. Eng. 4, 195–206 (2019). https://doi.org/10.1038/s41551-019-0486-02.7-fold survival increase with CAR-T-loaded Nitinol film vs untreatedFibrinMurine DCNoneYesMouse lung cancer model109109. V. Verma, Y. Kim, M.-C. Lee, J.-T. Lee, S. Cho, I.-K. Park et al., “ Activated dendritic cells delivered in tissue compatible biomatrices induce in-situ anti-tumor CTL responses leading to tumor regression,” Oncotarget 7(26), 39894–39906 (2016). https://doi.org/10.18632/oncotarget.9529Encapsulated DC treatment more effective than non-encapsulatedRADA16 peptideMurine DCTumor antigens, anti-PD-1NoMouse lymphoma model110110. P. Yang, H. Song, Y. Qin, P. Huang, C. Zhang, D. Kong et al., “ Engineering dendritic-cell-based vaccines and PD-1 blockade in self-assembled peptide nanofibrous hydrogel to amplify antitumor T-cell immunity,” Nano Lett. 18(7), 4377–4385 (2018). https://doi.org/10.1021/acs.nanolett.8b01406Survival improvement with gel-encapsulated DC vs untreated miceα-CD/PEGMurine DCDOX, CpG, B16 tumor cellsYesMouse melanoma model111111. A. Yang, X. Dong, Y. Bai, S. Sheng, Y. Zhang, T. Liu et al., “ Doxorubicin/CpG self-assembled nanoparticles prodrug and dendritic cells co-laden hydrogel for cancer chemo-assisted immunotherapy,” Chem. Eng. J. 416, 129192 (2021). https://doi.org/10.1016/j.cej.2021.129192,112112. A. Yang, Y. Bai, X. Dong, T. Ma, D. Zhu, L. Mei et al., “ Hydrogel/nanoadjuvant-mediated combined cell vaccines for cancer immunotherapy,” Acta Biomater. 133, 257–267 (2021). https://doi.org/10.1016/j.actbio.2021.08.014Significant survival improvement with gel-encapsulated DC with CpG + B16 vs single treatmentsGelatin-hydroxyphenyl propionic acidMurine DCOVYesMouse lung cancer model113113. E. Oh, J.-E. Oh, J. Hong, Y. Chung, Y. Lee, K. D. Park et al., “ Optimized biodegradable polymeric reservoir-mediated local and sustained co-delivery of dendritic cells and oncolytic adenovirus co-expressing IL-12 and GM-CSF for cancer immunotherapy,” J. Controlled Release 259, 115–127 (2017). https://doi.org/10.1016/j.jconrel.2017.03.028Increased survival compared to single treatments of DC/OVHyaluronic acidHuman CAR NK cellsNoneNoMouse leukemia and breast cancer models114114. Y. H. Ahn, L. Ren, S. M. Kim, S.-H. Seo, C.-R. Jung, D. S. Kim et al., “ A three-dimensional hyaluronic acid-based niche enhances the therapeutic efficacy of human natural killer cell-based cancer immunotherapy,” Biomaterials 247, 119960 (2020). https://doi.org/10.1016/j.biomaterials.2020.119960Significant survival improvement with gel-encapsulated CAR NK vs non-encapsulated NKAlginate microspheresHuman CAR-T cellsIL-15, hemoglobinYesMouse renal and ovarian cancer models115115. Z. Luo, Z. Liu, Z. Liang, J. Pan, J. Xu, J. Dong et al., “ Injectable porous microchips with oxygen reservoirs and an immune-niche enhance the efficacy of CAR T cell therapy in solid tumors,” ACS Appl. Mater. Interfaces 12(51), 56712–56722 (2020). https://doi.org/10.1021/acsami.0c15239Greatly improved mouse survival with alginate-encapsulated CAR-T cells compared to untreated miceFibrinHuman CAR-T cellsNoneNoMouse lymphoma and glioma models116116. E. A. Ogunnaike, A. Valdivia, M. Yazdimamaghani, E. Leon, S. Nandi, H. Hudson et al., “ Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma,” Sci. Adv. 7(41), eabg5841 (2021). https://doi.org/10.1126/sciadv.abg5841Significantly improved mouse survival with fibrin-encapsulated CAR-T cells compared to mice treated with non-encapsulated CAR-T cellsMethacrylated hyaluronic acidHuman CAR-T cellsIL-15 nanoparticles, anti-PD-L1 plateletsNoMouse model of human melanoma117117. Q. Hu, H. Li, E. Archibong, Q. Chen, H. Ruan, S. Ahn et al., “ Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets,” Nat. Biomed. Eng. 5(9), 1038–1047 (2021). https://doi.org/10.1038/s41551-021-00712-1Extensive tumor elimination with CAR + IL-15 + anti-PD-L1AlginateMonocytesTumor antigens, anti-PD-1Yes

Mouse breast cancer modelSignificant preventative and therapeutic anti-tumor effects

118118. Y. Tian, C. Xu, J. Feng, Y. Huangfu, K. Wang, and Z.-L. Zhang, “ Personalized gel-droplet monocyte vaccines for cancer immunotherapy,” Lab Chip 21(22), 4414–4426 (2021). https://doi.org/10.1039/D1LC00646K