Maude, S. L. et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N. Engl. J. Med. 378, 439–448 (2018).
Neelapu, S. S. et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N. Engl. J. Med. 377, 2531–2544 (2017).
Schuster, S. J. et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N. Engl. J. Med. 377, 2545–2554 (2017).
Beatty, G. L. et al. Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology 155, 29–32 (2018).
Hou, A. J., Chen, L. C. & Chen, Y. Y. Navigating CAR-T cells through the solid-tumour microenvironment. Nat. Rev. Drug Discov. 20, 531–550 (2021).
Newick, K., O’Brien, S., Moon, E. & Albelda, S. M. CAR T cell therapy for solid tumors. Annu. Rev. Med. 68, 139–152 (2017).
Beatty, G. L. et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce antitumor activity in solid malignancies. Cancer Immunol. Res. 2, 112–120 (2014).
Haas, A. R. et al. Phase I study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers. Mol. Ther. 27, 1919–1929 (2019).
Maus, M. V. et al. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol. Res. 1, 26–31 (2013).
Nagarsheth, N., Wicha, M. S. & Zou, W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat. Rev. Immunol. 17, 559–572 (2017).
Valkenburg, K. C., de Groot, A. E. & Pienta, K. J. Targeting the tumour stroma to improve cancer therapy. Nat. Rev. Clin. Oncol. 15, 366–381 (2018).
Lesch, S. et al. T cells armed with C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours. Nat. Biomed. Eng. 5, 1246–1260 (2021).
Albelda, S. M. CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn. Nat. Rev. Clin. Oncol. 21, 47–66 (2024).
Ho, W. J., Jaffee, E. M. & Zheng, L. The tumour microenvironment in pancreatic cancer—clinical challenges and opportunities. Nat. Rev. Clin. Oncol. 17, 527–540 (2020).
Pandol, S., Edderkaoui, M., Gukovsky, I., Lugea, A. & Gukovskaya, A. Desmoplasia of pancreatic ductal adenocarcinoma. Clin. Gastroenterol. Hepatol. 7, S44–S47 (2009).
Blando, J. et al. Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer. Proc. Natl Acad. Sci. USA 116, 1692–1697 (2019).
Tian, C. et al. Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveal different contributions by tumor and stromal cells. Proc. Natl Acad. Sci. USA 116, 19609–19618 (2019).
Watt, J. & Kocher, H. M. The desmoplastic stroma of pancreatic cancer is a barrier to immune cell infiltration. OncoImmunology https://doi.org/10.4161/onci.26788 (2014).
Cox, T. R. The matrix in cancer. Nat. Rev. Cancer 21, 217–238 (2021).
Peranzoni, E., Rivas-Caicedo, A., Bougherara, H., Salmon, H. & Donnadieu, E. Positive and negative influence of the matrix architecture on antitumor immune surveillance. Cell. Mol. Life Sci. 70, 4431–4448 (2013).
Acerbi, I. et al. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr. Biol. 7, 1120–1134 (2015).
Sahai, E. et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 20, 174–186 (2020).
Rhim, A. D. et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell 25, 735–747 (2014).
Biasci, D. et al. CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response. Proc. Natl Acad. Sci. USA 117, 28960–28970 (2020).
Bockorny, B. et al. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat. Med. 26, 878–885 (2020).
Feig, C. et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc. Natl Acad. Sci. USA 110, 20212–20217 (2013).
Ene-Obong, A. et al. Activated pancreatic stellate cells sequester CD8+ T cells to reduce their infiltration of the juxtatumoral compartment of pancreatic ductal adenocarcinoma. Gastroenterology 145, 1121–1132 (2013).
Wang, Z. et al. Carcinomas assemble a filamentous CXCL12-keratin-19 coating that suppresses T cell-mediated immune attack. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2119463119 (2022).
Dolor, A. & Szoka, F. C. Digesting a path forward: the utility of collagenase tumor treatment for improved drug delivery. Mol. Pharm. 15, 2069–2083 (2018).
Zinger, A. et al. Collagenase nanoparticles enhance the penetration of drugs into pancreatic tumors. ACS Nano 13, 11008–11021 (2019).
Wang, L. et al. Enhanced intracellular transcytosis of nanoparticles by degrading extracellular matrix for deep tissue radiotherapy of pancreatic adenocarcinoma. Nano Lett. 22, 6877–6887 (2022).
Zhou, N. et al. Exploring the stereochemistry of CXCR4-peptide recognition and inhibiting HIV-1 entry with d-peptides derived from chemokines. J. Biol. Chem. 277, 17476–17485 (2002).
Ansari, S., Mudassir, M., Vijayalekshmi, B. & Chattopadhyay, P. Targeting CXCR4-expressing cancer cells with avidin-poly (lactic-co-glycolic acid) nanoparticle surface modified with biotinylated DV1 peptide. Int. J. Appl. Basic Med. Res. 13, 106–112 (2023).
Houg, D. S. & Bijlsma, M. F. The hepatic pre-metastatic niche in pancreatic ductal adenocarcinoma. Mol. Cancer https://doi.org/10.1186/s12943-018-0842-9 (2018).
Saur, D. et al. CXCR4 expression increases liver and lung metastasis in a mouse model of pancreatic cancer. Gastroenterology 129, 1237–1250 (2005).
Xie, Y. et al. Stromal modulation and treatment of metastatic pancreatic cancer with local intraperitoneal triple miRNA/siRNA nanotherapy. ACS Nano 14, 255–271 (2020).
Zhao, H. & Heindel, N. D. Determination of degree of substitution of formyl groups in polyaldehyde dextran by the hydroxylamine hydrochloride method. Pharm. Res. 8, 400–402 (1991).
Qian, D. et al. Galectin-1-driven upregulation of SDF-1 on pancreatic stellate cells promotes pancreatic cancer metastasis. Cancer Lett. 397, 43–51 (2017).
Kato, M., Hattori, Y., Kubo, M. & Maitani, Y. Collagenase-1 injection improved tumor distribution and gene expression of cationic lipoplex. Int. J. Pharm. 423, 428–434 (2012).
Diener, B., Carrick, L. Jr. & Berk, R. S. In vivo studies with collagenase from Pseudomonas aeruginosa. Infect. Immun. 7, 212–217 (1973).
Rosenberg, S. A. & Restifo, N. P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348, 62–68 (2015).
Wehrli, M. et al. Mesothelin CAR T cells secreting anti-FAP/anti-CD3 molecules efficiently target pancreatic adenocarcinoma and its stroma. Clin. Cancer Res. 30, 1859–1877 (2024).
Lee, H. H. et al. Therapeutic efficacy of T cells expressing chimeric antigen receptor derived from a mesothelin-specific scFv in orthotopic human pancreatic cancer animal models. Neoplasia 24, 98–108 (2022).
Adler-Nissen, J. Determination of the degree of hydrolysis of food protein hydrolysates by trinitrobenzenesulfonic acid. J. Agric. Food Chem. 27, 1256–1262 (1979).
