Addressing the obstacles of CAR T cell migration in solid tumors: wishing a heavy traffic

References

• Titov A, Zmievskaya E, Ganeeva I, et al. Adoptive immunotherapy beyond CAR T-cells. Cancers. 2021;13(4):743.
   PubMed Web of Science ®Google Scholar
• Larson RC, Maus MV. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat Rev Cancer. 2021;21(3):145–161.
   PubMed Web of Science ®Google Scholar
• Mullard A. FDA approves first CAR T therapy. Nat Rev Drug Discov. 2017;16(10):669–669.
   Web of Science ®Google Scholar
• FDA approves second CAR T-cell therapy. Cancer Dis. 2018;8(1):5–6.
   Web of Science ®Google Scholar
• Voelker R. CAR-T therapy is approved for mantle cell lymphoma. JAMA. 2020;324(9):832.
   Web of Science ®Google Scholar
• Hashem Boroojerdi M, Rahbarizadeh F, Safarzadeh Kozani P, et al. Strategies for having a more effective and less toxic CAR T-cell therapy for acute lymphoblastic leukemia. Med Oncol. 2020;37(11):100.
   PubMed Web of Science ®Google Scholar
• Mullard A. FDA approves first BCMA-targeted CAR-T cell therapy. Nat Rev Drug Discov. 2021;20(5):332.
   Web of Science ®Google Scholar
• Mullard A. FDA approves fourth CAR-T cell therapy. Nat Rev Drug Discov. 2021;20(3):166.
   Web of Science ®Google Scholar
• Safarzadeh Kozani P, Safarzadeh Kozani P, Rahbarizadeh F. Novel antigens of CAR T cell therapy: new roads; old destination. Transl Oncol. 2021;14(7):101079.
   PubMed Web of Science ®Google Scholar
• Safarzadeh Kozani P, Safarzadeh Kozani P, O'Connor RS. In like a lamb; out like a lion: marching CAR T cells toward enhanced efficacy in B-ALL. Mol Cancer Ther. 2021;20(7):1223–1233.
   Google Scholar
• Safarzadeh Kozani P, Safarzadeh Kozani P, Rahbarizadeh F, et al. Strategies for dodging the obstacles in CAR T cell therapy. Front Oncol. 2021;11(924):627549.
   PubMedGoogle Scholar
• Jamnani FR, Rahbarizadeh F, Shokrgozar MA, et al. T cells expressing VHH-directed oligoclonal chimeric HER2 antigen receptors: towards tumor-directed oligoclonal T cell therapy. Biochim Biophys Acta. 2014;1840(1):378–386.
   PubMed Web of Science ®Google Scholar
• Sharifzadeh Z, Rahbarizadeh F, Shokrgozar MA, et al. Genetically engineered T cells bearing chimeric nanoconstructed receptors harboring TAG-72-specific camelid single domain antibodies as targeting agents. Cancer Lett. 2013;334(2):237–244.
   PubMed Web of Science ®Google Scholar
• Rahbarizadeh F, Ahmadvand D, Moghimi SM. CAR T-cell bioengineering: single variable domain of heavy chain antibody targeted CARs. Adv Drug Deliv Rev. 2019;141:41–46.
   PubMed Web of Science ®Google Scholar
• Wang Y, Xu Y, Li S, et al. Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells. J Hematol Oncol. 2018;11(1):60.
   PubMed Web of Science ®Google Scholar
• Wang D, Starr R, Chang WC, et al. Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma. Sci Transl Med. 2020;12(533):eaaw2672.
   PubMed Web of Science ®Google Scholar
• Stoiber S, Cadilha BL, Benmebarek M-R, et al. Limitations in the design of chimeric antigen receptors for cancer therapy. Cells. 2019;8(5):472.
   PubMed Web of Science ®Google Scholar
• Collinson-Pautz MR, Chang W-C, Lu A, et al. Constitutively active MyD88/CD40 costimulation enhances expansion and efficacy of chimeric antigen receptor T cells targeting hematological malignancies. Leukemia. 2019;33(9):2195–2207.
   PubMed Web of Science ®Google Scholar
• Wang E, Wang L-C, Tsai C-Y, et al. Generation of potent T-cell immunotherapy for cancer using DAP12-Based, multichain, chimeric immunoreceptors. Cancer Immunol Res. 2015;3(7):815–826.
   PubMed Web of Science ®Google Scholar
• Guedan S, Madar A, Casado-Medrano V, et al. Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability. J Clin Invest. 2020;130(6):3087–3097.
   PubMed Web of Science ®Google Scholar
• Caratelli S, Sconocchia T, Arriga R, et al. FCγ chimeric receptor-engineered T cells: methodology, advantages, limitations, and clinical relevance. Front Immunol. 2017;8:457.
   PubMed Web of Science ®Google Scholar
• Karlsson H, Svensson E, Gigg C, et al. Evaluation of intracellular signaling downstream chimeric antigen receptors. PLoS One. 2015;10(12):e0144787.
   PubMed Web of Science ®Google Scholar
• Ng Y-Y, Tay JCK, Li Z, et al. T cells expressing NKG2D CAR with a DAP12 signaling domain stimulate lower cytokine production while being effective in tumor eradication. Mol Ther. 2021;29(1):75–85.
   PubMed Web of Science ®Google Scholar
• van der Stegen SJ, Hamieh M, Sadelain M. The pharmacology of second-generation chimeric antigen receptors. Nat Rev Drug Discov. 2015;14(7):499–509.
   PubMed Web of Science ®Google Scholar
• Zhong X-S, Matsushita M, Plotkin J, et al. Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/AKT/Bcl-XL activation and CD8+ T cell-mediated tumor eradication. Mol Ther. 2010;18(2):413–420.
   PubMed Web of Science ®Google Scholar
• Duell J, Lurati S, Dittrich M, et al. First generation chimeric antigen receptor display functional defects in key signal pathways upon antigen stimulation. Blood. 2010;116(21):2088–2088.
   Web of Science ®Google Scholar
• Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther. 2015;15(8):1145–1154.
   PubMed Web of Science ®Google Scholar
• Tokarew N, Ogonek J, Endres S, et al. Teaching an old dog new tricks: next-generation CAR T cells. Br J Cancer. 2019;120(1):26–37.
   PubMed Web of Science ®Google Scholar
• Parker KR, Migliorini D, Perkey E, et al. Single-cell analyses identify brain mural cells expressing CD19 as potential off-tumor targets for CAR-T immunotherapies. Cell. 2020;183(1):126–142.e17.
   PubMed Web of Science ®Google Scholar
• Bernhard H, Neudorfer J, Gebhard K, et al. Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer. Cancer Immunol Immunother. 2008;57(2):271–280.
   PubMed Web of Science ®Google Scholar
• Klein D. The tumor vascular endothelium as decision maker in cancer therapy. Front Oncol. 2018;8:367–367.
   PubMed Web of Science ®Google Scholar
• Piali L, Fichtel A, Terpe HJ, et al. Endothelial vascular cell adhesion molecule 1 expression is suppressed by melanoma and carcinoma. J Exp Med. 1995;181(2):811–816.
   PubMed Web of Science ®Google Scholar
• Griffioen AW, Damen CA, Blijham GH, et al. Tumor angiogenesis is accompanied by a decreased inflammatory response of tumor-associated endothelium. Blood. 1996;88(2):667–673.
   PubMed Web of Science ®Google Scholar
• Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol. 2005;7(4):452–464.
   PubMed Web of Science ®Google Scholar
• Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015;348(6230):74–80.
   PubMed Web of Science ®Google Scholar
• Salmon H, Franciszkiewicz K, Damotte D, et al. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J Clin Invest. 2012;122(3):899–910.
   PubMed Web of Science ®Google Scholar
• Yamauchi M, Barker TH, Gibbons DL, et al. The fibrotic tumor stroma. J Clin Invest. 2018;128(1):16–25.
   PubMed Web of Science ®Google Scholar
• Peranzoni E, Lemoine J, Vimeux L, et al. Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment. Proc Natl Acad Sci U S A. 2018;115(17):E4041–E4050.
   PubMed Web of Science ®Google Scholar
• Sugiura A, Rathmell JC. Metabolic barriers to T cell function in tumors. J Immunol. 2018;200(2):400–407.
   PubMed Web of Science ®Google Scholar
• Jayaprakash P, Ai M, Liu A, et al. Targeted hypoxia reduction restores T cell infiltration and sensitizes prostate cancer to immunotherapy. J Clin Invest. 2018;128(11):5137–5149.
   PubMed Web of Science ®Google Scholar
• Manaster Y, Shipony Z, Hutzler A, et al. Reduced CTL motility and activity in avascular tumor areas. Cancer Immunol Immunother. 2019;68(8):1287–1301.
   PubMed Web of Science ®Google Scholar
• Kawalekar OU, O’Connor RS, Fraietta JA, et al. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity. 2016;44(2):380–390.
   PubMed Web of Science ®Google Scholar
• Mollica Poeta M, Massara M, Capucetti A, et al. Chemokines and chemokine receptors: new targets for cancer immunotherapy. Front Immunol. 2019;10:379.
   PubMed Web of Science ®Google Scholar
• Dangaj D, Bruand M, Grimm AJ, et al. Cooperation between constitutive and inducible chemokines enables T cell engraftment and immune attack in solid tumors. Cancer Cell. 2019;35(6):885–900.e10.
   PubMed Web of Science ®Google Scholar
• Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature. 2015;523(7559):231–235.
   PubMed Web of Science ®Google Scholar
• Li X, Xiang Y, Li F, et al. WNT/β-catenin signaling pathway regulating T cell-inflammation in the tumor microenvironment. Front Immunol. 2019;10:2293–2293.
   PubMed Web of Science ®Google Scholar
• Kaler P, Augenlicht L, Klampfer L. Macrophage-derived IL-1beta stimulates wnt signaling and growth of colon cancer cells: a crosstalk interrupted by vitamin D3. Oncogene. 2009;28(44):3892–3902.
   PubMed Web of Science ®Google Scholar
• Feig C, Jones JO, Kraman M, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A. 2013;110(50):20212–20217.
   PubMed Web of Science ®Google Scholar
• Fischer J, Paret C, El Malki K, et al. CD19 isoforms enabling resistance to CART-19 immunotherapy are expressed in B-ALL patients at initial diagnosis. J Immunother. 2017;40(5):187–195.
   PubMed Web of Science ®Google Scholar
• Fry TJ, Shah NN, Orentas RJ, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018;24(1):20–28.
   PubMed Web of Science ®Google Scholar
• O'Rourke DM, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9(399):eaaa0984.
   PubMed Web of Science ®Google Scholar
• Choi BD, Yu X, Castano AP, et al. CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity. Nat Biotechnol. 2019;37(9):1049–1058.
   PubMed Web of Science ®Google Scholar
• Li W, Qiu S, Chen J, et al. Chimeric antigen receptor designed to prevent ubiquitination and downregulation showed durable antitumor efficacy. Immunity. 2020;53(2):456–470.e6.
   PubMed Web of Science ®Google Scholar
• Cazaux M, Grandjean CL, Lemaître F, et al. Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity. J Exp Med. 2019;216(5):1038–1049.
   PubMed Web of Science ®Google Scholar
• Lee Y, Auh SL, Wang Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009;114(3):589–595.
   PubMed Web of Science ®Google Scholar
• Seyedin SN, Schoenhals JE, Lee DA, et al. Strategies for combining immunotherapy with radiation for anticancer therapy. Immunotherapy. 2015;7(9):967–980.
   PubMed Web of Science ®Google Scholar
• Dovedi SJ, Cheadle EJ, Popple AL, et al. Fractionated radiation therapy stimulates antitumor immunity mediated by both resident and infiltrating polyclonal T-cell populations when combined with PD-1 blockade. Clin Cancer Res. 2017;23(18):5514–5526.
   PubMed Web of Science ®Google Scholar
• Xu J, Wang Y, Shi J, et al. Combination therapy: a feasibility strategy for CAR-T cell therapy in the treatment of solid tumors. Oncol Lett. 2018;16(2):2063–2070.
   PubMed Web of Science ®Google Scholar
• Smith EL, Mailankody S, Staehr M, et al. BCMA-targeted CAR T-cell therapy plus radiotherapy for the treatment of refractory myeloma reveals potential synergy. Cancer Immunol Res. 2019;7(7):1047–1053.
   PubMed Web of Science ®Google Scholar
• Weiss T, Weller M, Guckenberger M, et al. NKG2D-based CAR T cells and radiotherapy exert synergistic efficacy in glioblastoma. Cancer Res. 2018;78(4):1031–1043.
   PubMed Web of Science ®Google Scholar
• Gattinoni L, Finkelstein SE, Klebanoff CA, et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med. 2005;202(7):907–912.
   PubMed Web of Science ®Google Scholar
• Ninomiya S, Narala N, Huye L, et al. Tumor indoleamine 2,3-dioxygenase (IDO) inhibits CD19-CAR T cells and is downregulated by lymphodepleting drugs. Blood. 2015;125(25):3905–3916.
   PubMed Web of Science ®Google Scholar
• Gao Q, Wang S, Chen X, et al. Cancer-cell-secreted CXCL11 promoted CD8(+) T cells infiltration through docetaxel-induced-release of HMGB1 in NSCLC. J Immunother Cancer. 2019;7(1):42.
   PubMed Web of Science ®Google Scholar
• Srivastava S, et al. Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade. Cancer Cell. 2021;39:193–208.e10.
   PubMed Web of Science ®Google Scholar
• Bocca P, Di Carlo E, Caruana I, et al. Bevacizumab-mediated tumor vasculature remodelling improves tumor infiltration and antitumor efficacy of GD2-CAR T cells in a human neuroblastoma preclinical model. Oncoimmunology. 2017;7(1):e1378843.
   PubMed Web of Science ®Google Scholar
• Deng C, Zhao J, Zhou S, et al. The vascular disrupting agent CA4P improves the antitumor efficacy of CAR-T cells in preclinical models of solid human tumors. Mol Ther. 2020;28(1):75–88.
   PubMed Web of Science ®Google Scholar
• Wu X, Luo H, Shi B, et al. Combined antitumor effects of sorafenib and GPC3-CAR T cells in mouse models of hepatocellular carcinoma. Mol Ther. 2019;27(8):1483–1494.
   PubMed Web of Science ®Google Scholar
• Li H, Ding J, Lu M, et al. CAIX-specific CAR-T cells and sunitinib show synergistic effects against metastatic renal cancer models. J Immunother. 2020;43(1):16–28.
   PubMed Web of Science ®Google Scholar
• Pàez-Ribes M, Allen E, Hudock J, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009;15(3):220–231.
   PubMed Web of Science ®Google Scholar
• Ebos JML, Lee CR, Cruz-Munoz W, et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009;15(3):232–239.
   PubMed Web of Science ®Google Scholar
• Raghav KP, Blumenschein GR. Motesanib and advanced NSCLC: experiences and expectations. Expert Opin Investig Drugs. 2011;20(6):859–869.
   PubMed Web of Science ®Google Scholar
• Bellesoeur A, Carton E, Alexandre J, et al. Axitinib in the treatment of renal cell carcinoma: design, development, and place in therapy. Drug Des Devel Ther. 2017;11:2801–2811.
   PubMed Web of Science ®Google Scholar
• Morabito A, Piccirillo MC, Costanzo R, et al. Vandetanib: an overview of its clinical development in NSCLC and other tumors. Drugs Today (Barc). 2010; 46(9):683–698.
   PubMed Web of Science ®Google Scholar
• Gan HK, Seruga B, Knox JJ. Sunitinib in solid tumors. Expert Opin Investig Drugs. 2009;18(6):821–834.
   PubMed Web of Science ®Google Scholar
• Dietrich J, Wang D, Batchelor TT. Cediranib: profile of a novel anti-angiogenic agent in patients with glioblastoma. Expert Opin Investig Drugs. 2009;18(10):1549–1557.
   PubMed Web of Science ®Google Scholar
• Keating GM, Santoro A. Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs. 2009;69(2):223–240.
   PubMed Web of Science ®Google Scholar
• Scott EN, Meinhardt G, Jacques C, et al. Vatalanib: the clinical development of a tyrosine kinase inhibitor of angiogenesis in solid tumours. Expert Opin Investig Drugs. 2007;16(3):367–379.
   PubMed Web of Science ®Google Scholar
• Sloan B, Scheinfeld NS. Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy. Curr Opin Investig Drugs. 2008;9(12):1324–1335.
   PubMed Web of Science ®Google Scholar
• Keating GM. Bevacizumab: a review of its use in advanced cancer. Drugs. 2014;74(16):1891–1925.
   PubMed Web of Science ®Google Scholar
• Poole RM, Vaidya A. Ramucirumab: first global approval. Drugs. 2014;74(9):1047–1058.
   PubMed Web of Science ®Google Scholar
• Gaya A, Tse V. A preclinical and clinical review of aflibercept for the management of cancer. Cancer Treat Rev. 2012;38(5):484–493.
   PubMed Web of Science ®Google Scholar
• Berahovich R, Liu X, Zhou H, et al. Hypoxia selectively impairs CAR-T cells in vitro. Cancers (Basel). 2019;11(5):602.
   Web of Science ®Google Scholar
• Juillerat A, Marechal A, Filhol JM, et al. An oxygen sensitive self-decision making engineered CAR T-cell. Sci Rep. 2017;7:39833.
   PubMed Web of Science ®Google Scholar
• Liao Q, He H, Mao Y, et al. Engineering T cells with hypoxia-inducible chimeric antigen receptor (HiCAR) for selective tumor killing. Biomark Res. 2020;8(1):56.
   PubMed Web of Science ®Google Scholar
• Ohta A, Gorelik E, Prasad SJ, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A. 2006;103(35):13132–13137.
   PubMed Web of Science ®Google Scholar
• Ohta A, Sitkovsky M. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature. 2001;414(6866):916–920.
   PubMed Web of Science ®Google Scholar
• Allard B, Pommey S, Smyth MJ, et al. Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs. Clin Cancer Res. 2013;19(20):5626–5635.
   PubMed Web of Science ®Google Scholar
• Young A, Ngiow SF, Barkauskas DS, et al. Co-inhibition of CD73 and A2AR adenosine signaling improves anti-tumor immune responses. Cancer Cell. 2016;30(3):391–403.
   PubMed Web of Science ®Google Scholar
• Halpin-Veszeleiova K, Hatfield SM. Oxygenation and A2AR blockade to eliminate hypoxia/HIF-1α-adenosinergic immunosuppressive axis and improve cancer immunotherapy. Curr Opin Pharmacol. 2020;53:84–90.
   PubMed Web of Science ®Google Scholar
• Chinnasamy D, Yu Z, Kerkar SP, et al. Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin Cancer Res. 2012;18(6):1672–1683.
   PubMed Web of Science ®Google Scholar
• Chinnasamy D, Tran E, Yu Z, et al. Simultaneous targeting of tumor antigens and the tumor vasculature using T lymphocyte transfer synergize to induce regression of established tumors in mice. Cancer Res. 2013;73(11):3371–3380.
   PubMed Web of Science ®Google Scholar
• Fu X, Rivera A, Tao L, et al. Genetically modified T cells targeting neovasculature efficiently destroy tumor blood vessels, shrink established solid tumors and increase nanoparticle delivery. Int J Cancer. 2013;133(10):2483–2492.
   PubMed Web of Science ®Google Scholar
• Santoro SP, Kim S, Motz GT, et al. T cells bearing a chimeric antigen receptor against prostate-specific membrane antigen mediate vascular disruption and result in tumor regression. Cancer Immunol Res. 2015;3(1):68–84.
   PubMed Web of Science ®Google Scholar
• Zhuang X, Maione F, Robinson J, et al. CAR T cells targeting tumor endothelial marker CLEC14A inhibit tumor growth. JCI Insight. 2020;5(19):e138808.
   PubMed Web of Science ®Google Scholar
• Alfaro C, Teijeira A, Oñate C, et al. Tumor-produced interleukin-8 attracts human myeloid-derived suppressor cells and elicits extrusion of neutrophil extracellular traps (NETs). Clin Cancer Res. 2016;22(15):3924–3936.
   PubMed Web of Science ®Google Scholar
• Ning Y, Manegold PC, Hong YK, et al. Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in Colon cancer cell line models. Int J Cancer. 2011;128(9):2038–2049.
   PubMed Web of Science ®Google Scholar
• Legler DF, Johnson-Léger C, Wiedle G, et al. The alpha v beta 3 integrin as a tumor homing ligand for lymphocytes. Eur J Immunol. 2004;34(6):1608–1616.
   PubMed Web of Science ®Google Scholar
• Di Stasi A, De Angelis B, Rooney CM, et al. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood. 2009;113(25):6392–6402.
   PubMed Web of Science ®Google Scholar
• Craddock JA, Lu A, Bear A, et al. Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. J Immunother. 2010;33(8):780–788.
   PubMed Web of Science ®Google Scholar
• Moon EK, Carpenito C, Sun J, et al. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor. Clin Cancer Res. 2011;17(14):4719–4730.
   PubMed Web of Science ®Google Scholar
• Moon EK, Wang L-CS, Bekdache K, et al. Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines. Oncoimmunology. 2018;7(3):e1395997.
   PubMed Web of Science ®Google Scholar
• Jin L, Tao H, Karachi A, et al. CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. Nat Commun. 2019;10(1):4016.
   PubMed Web of Science ®Google Scholar
• Whilding L, Halim L, Draper B, et al. CAR T-cells targeting the integrin αvβ6 and co-expressing the chemokine receptor CXCR2 demonstrate enhanced homing and efficacy against several solid malignancies. Cancers (Basel). 2019;11(5):674.
   PubMed Web of Science ®Google Scholar
• Nellan A, Rota C, Majzner R, et al. Durable regression of medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells. J Immunother Cancer. 2018;6(1):30.
   PubMed Web of Science ®Google Scholar
• Priceman SJ, Tilakawardane D, Jeang B, et al. Regional delivery of chimeric antigen receptor-engineered T cells effectively targets HER2(+) breast cancer metastasis to the brain. Clin Cancer Res. 2018;24(1):95–105.
   PubMed Web of Science ®Google Scholar
• Katz SC, Point GR, Cunetta M, et al. Regional CAR-T cell infusions for peritoneal carcinomatosis are superior to systemic delivery. Cancer Gene Ther. 2016;23(5):142–148.
   PubMed Web of Science ®Google Scholar
• Murad JP, Kozlowska AK, Lee HJ, et al. Effective targeting of TAG72(+) peritoneal ovarian tumors via regional delivery of CAR-engineered T cells. Front Immunol. 2018;9:2268.
   PubMed Web of Science ®Google Scholar
• Donovan LK, Delaidelli A, Joseph SK, et al. Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma. Nat Med. 2020;26(5):720–731.
   PubMed Web of Science ®Google Scholar
• Theruvath J, Sotillo E, Mount CW, et al. Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. Nat Med. 2020;26(5):712–719.
   PubMed Web of Science ®Google Scholar
• Chen Q, Hu Q, Dukhovlinova E, et al. Photothermal therapy promotes tumor infiltration and antitumor activity of CAR T cells. Adv Mater. 2019;31(23):e1900192.
   PubMed Web of Science ®Google Scholar
• Parihar R, Rivas C, Huynh M, et al. NK cells expressing a chimeric activating receptor eliminate MDSCs and rescue impaired CAR-T cell activity against solid tumors. Cancer Immunol Res. 2019;7(3):363–375.
   PubMed Web of Science ®Google Scholar
• Lee JM, Lee M-H, Garon E, et al. Phase I trial of intratumoral injection of CCL21 gene-modified dendritic cells in lung cancer elicits tumor-specific immune responses and CD8+ T-cell Infiltration. Clin Cancer Res. 2017;23(16):4556–4568.
   PubMed Web of Science ®Google Scholar
• Caruana I, Savoldo B, Hoyos V, et al. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat Med. 2015;21(5):524–529.
   PubMed Web of Science ®Google Scholar
• Jin X, Xu Q, Pu C, et al. Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. Cell Mol Immunol. 2021;18(8):1896–1903.,
   PubMed Web of Science ®Google Scholar
• Amor C, Feucht J, Leibold J, et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature. 2020;583(7814):127–132.
   PubMed Web of Science ®Google Scholar
• Herzig E, Kim KC, Packard TA, et al. Attacking latent HIV with convertible CAR-T cells, a highly adaptable killing platform. Cell. 2019;179(4):880–894.e10.
   PubMed Web of Science ®Google Scholar
• Shrestha B, Walton K, Reff J, et al. Human CD83-targeted chimeric antigen receptor T cells prevent and treat graft-versus-host disease. J Clin Invest. 2020;130(9):4652–4662.
   PubMed Web of Science ®Google Scholar
• Wallstabe L, Göttlich C, Nelke LC, et al. ROR1-CAR T cells are effective against lung and breast cancer in advanced microphysiologic 3D tumor models. JCI Insight. 2019;4(18):e126345.
   PubMed Web of Science ®Google Scholar
• Jacob F, Salinas RD, Zhang DY, et al. A patient-derived glioblastoma organoid model and biobank recapitulates inter- and intra-tumoral heterogeneity. Cell. 2020;180(1):188–204.e22.
   PubMed Web of Science ®Google Scholar
• Mulazzani M, Fräßle SP, von Mücke-Heim I, et al. Long-term in vivo microscopy of CAR T cell dynamics during eradication of CNS lymphoma in mice. Proc Natl Acad Sci U S A. 2019;116(48):24275–24284.
   PubMed Web of Science ®Google Scholar
• Sellmyer MA, Richman SA, Lohith K, et al. Imaging CAR T cell trafficking with eDHFR as a PET reporter gene. Mol Ther. 2020;28(1):42–51.
   PubMed Web of Science ®Google Scholar
• Emami-Shahri N, Foster J, Kashani R, et al. Clinically compliant spatial and temporal imaging of chimeric antigen receptor T-cells. Nat Commun. 2018;9(1):1081.
   PubMedGoogle Scholar