Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity

Science Translational Medicine

Volumn 6, Issue 261, 2014, Pages

  Adusumilli, Prasad S ^a   Cherkassky, Leonid ^a   Villena Vargas, Jonathan ^a   Colovos, Christos ^a   Servais, Elliot ^a   Plotkin, Jason ^a   Jones, David R ^a   Sadelain, Michel ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHIMERIC ANTIGEN RECEPTOR; CHIMERIC ANTIGEN RECEPTOR M28Z; CHIMERIC ANTIGEN RECEPTOR MZ; CHIMERIC ANTIGEN RECEPTOR P28Z; INTERLEUKIN 2; MESOTHELIN; RETROVIRUS VECTOR; UNCLASSIFIED DRUG; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN RECOGNITION; ANTIGEN SPECIFICITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER GENE THERAPY; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CD4 CD8 RATIO; CD4+ T LYMPHOCYTE; CELL EXPANSION; CELL MEDIATED CYTOTOXICITY; CELL THERAPY; CONTROLLED STUDY; DISEASE ERADICATION; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INTRAPLEURAL T CELL THERAPY; INTRAVENOUS T CELL THERAPY; LYMPHOCYTE DIFFERENTIATION; MOUSE; NONHUMAN; PLEURA TUMOR; PROTEIN TARGETING; SINGLE DRUG DOSE; SOLID TUMOR; SYSTEMIC THERAPY; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TREATMENT RESPONSE; TUMOR IMMUNITY; TUMOR REGRESSION; VIRAL GENE DELIVERY SYSTEM; ADOPTIVE IMMUNOTHERAPY; ANIMAL; BIOSYNTHESIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CHIMERA; CYTOTOXICITY; DRUG SCREENING; GENE THERAPY; GENETIC TRANSDUCTION; GENETICS; HEK293 CELL LINE; IMMUNOLOGY; LUNG NEOPLASMS; LYMPHOCYTE ACTIVATION; MESOTHELIOMA; METABOLISM; NONOBESE DIABETIC MOUSE; PATHOLOGY; PLEURAL NEOPLASMS; PROCEDURES; SCID MOUSE; TIME FACTOR; TRANSPLANTATION; TUMOR ASSOCIATED LEUKOCYTE; TUMOR CELL LINE;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; CELL LINE, TUMOR; CELL PROLIFERATION; CHIMERISM; CYTOTOXICITY, IMMUNOLOGIC; FEMALE; GENETIC THERAPY; GPI-LINKED PROTEINS; HEK293 CELLS; HUMANS; IMMUNOTHERAPY, ADOPTIVE; LUNG NEOPLASMS; LYMPHOCYTE ACTIVATION; LYMPHOCYTES, TUMOR-INFILTRATING; MESOTHELIOMA; MICE, INBRED NOD; MICE, SCID; PLEURAL NEOPLASMS; RECEPTORS, ANTIGEN, T-CELL; TIME FACTORS; TRANSDUCTION, GENETIC; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84908891854     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3010162     Document Type: Article

References (66)

1. V. B. Antony, R. Loddenkemper, P. Astoul, C. Boutin, P. Goldstraw, J. Hott, F. Rodriguez Panadero, S. A. Sahn, Management of malignant pleural effusions. Eur. Respir. J. 18, 402-419 (2001).
2. B. W. Robinson, A. W. Musk, R. A. Lake, Malignant mesothelioma. Lancet 366, 397-408 (2005).
3. M. Anraku, K. S. Cunningham, Z. Yun, M. S. Tsao, L. Zhang, S. Keshavjee, M. R. Johnston, M. De Perrot, Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma. J. Thorac. Cardiovasc. Surg. 135, 823-829 (2008).
4. + tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection. Cancer Immunol. Immunother. 59, 1543-1549 (2010).
5. K. Suzuki, K. Kadota, C. S. Sima, M. Sadelain, V. W. Rusch, W. D. Travis, P. S. Adusumilli, Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients. Cancer Immunol. Immunother. 60, 1721-1728 (2011).
6. A. J. Bograd, K. Suzuki, E. Vertes, C. Colovos, E. A. Morales, M. Sadelain, P. S. Adusumilli, Immune responses and immunotherapeutic interventions in malignant pleural mesothelioma. Cancer Immunol. Immunother. 60, 1509-1527 (2011).
7. P. S. Adusumilli, Translational immunotherapeutics: Chemoimmunotherapy for malignant pleural mesothelioma. Cancer 120, 3268-3271 (2014).
8. J. N. Kochenderfer, M. E. Dudley, R. O. Carpenter, S. H. Kassim, J. J. Rose, W. G. Telford, F. T. Hakim, D. C. Halverson, D. H. Fowler, N. M. Hardy, A. R. Mato, D. D. Hickstein, J. C. Gea-Banacloche, S. Z. Pavletic, C. Sportes, I. Maric, S. A. Feldman, B. G. Hansen, J. S. Wilder, B. Blacklock-Schuver, B. Jena, M. R. Bishop, R. E. Gress, S. A. Rosenberg, Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 122, 4129-4139 (2013).
9. R. J. Brentjens, M. L. Davila, I. Riviere, J. Park, X. Wang, L. G. Cowell, S. Bartido, J. Stefanski, C. Taylor, M. Olszewska, O. Borquez-Ojeda, J. Qu, T. Wasielewska, Q. He, Y. Bernal, I. V. Rijo, C. Hedvat, R. Kobos, K. Curran, P. Steinherz, J. Jurcic, T. Rosenblat, P. Maslak, M. Frattini, M. Sadelain, CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci. Transl. Med. 5, 177ra138 (2013)
10. S. A. Grupp, M. Kalos, D. Barrett, R. Aplenc, D. L. Porter, S. R. Rheingold, D. T. Teachey, A. Chew, B. Hauck, J. F. Wright, M. C. Milone, B. L. Levine, C. H. June, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N. Engl. J. Med. 368, 1509-1518 (2013).
11. M. L. Davila, I. Riviere, X. Wang, S. Bartido, J. Park, K. Curran, S. S. Chung, J. Stefanski, O. Borquez-Ojeda, M. Olszewska, J. Qu, T. Wasielewska, Q. He, M. Fink, H. Shinglot, M. Youssif, M. Satter, Y. Wang, J. Hosey, H. Quintanilla, E. Halton, Y. Bernal, D. C. Bouhassira, M. E. Arcila, M. Gonen, G. J. Roboz, P. Maslak, D. Douer, M. G. Frattini, S. Giralt, M. Sadelain, R. Brentjens, Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6, 224ra225 (2014).
12. M. Sadelain, R. Brentjens, I. Rivière, The basic principles of chimeric antigen receptor design. Cancer Discov. 3, 388-398 (2013).
13. M. C. Jensen, S. R. Riddell, Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells. Immunol. Rev. 257, 127-144 (2014).
14. E. L. Servais, C. Colovos, L. Rodriguez, A. J. Bograd, J. Nitadori, C. Sima, V. W. Rusch, M. Sadelain, P. S. Adusumilli, Mesothelin overexpression promotes mesothelioma cell invasion and MMP-9 secretion in an orthotopic mouse model and in epithelioid pleural mesothelioma patients. Clin. Cancer Res. 18, 2478-2489 (2012).
15. S. S. Kachala, A. J. Bograd, J. Villena-Vargas, K. Suzuki, E. L. Servais, K. Kadota, J. Chou, C. S. Sima, E. Vertes, V. W. Rusch, W. D. Travis, M. Sadelain, P. S. Adusumilli, Mesothelin overexpression is a marker of tumor aggressiveness and is associated with reduced recurrence-free and overall survival in early-stage lung adenocarcinoma. Clin. Cancer Res. 20, 1020-1028 (2014).
16. N. P. Rizk, E. L. Servais, L. H. Tang, C. S. Sima, H. Gerdes, M. Fleisher, V. W. Rusch, P. S. Adusumilli, Tissue and serum mesothelin are potential markers of neoplastic progression in Barrett's associated esophageal adenocarcinoma. Cancer Epidemiol. Biomarkers Prev. 21, 482-486 (2012).
17. J. Villena-Vargas, P. S. Adusumilli, Mesothelin-targeted immunotherapies for malignant pleural mesothelioma. Ann. Cardiothorac. Surg. 1, 466-471 (2012).
18. I. Pastan, R. Hassan, Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res. 74, 2907-2912 (2014).
19. R. Hassan, A. C. Miller, E. Sharon, A. Thomas, J. C. Reynolds, A. Ling, R. J. Kreitman, M. M. Miettinen, S. M. Steinberg, D. H. Fowler, I. Pastan, Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression. Sci. Transl. Med. 5, 208ra147 (2013).
20. C. Carpenito, M. C. Milone, R. Hassan, J. C. Simonet, M. Lakhal, M. M. Suhoski, A. Varela-Rohena, K. M. Haines, D. F. Heitjan, S. M. Albelda, R. G. Carroll, J. L. Riley, I. Pastan, C. H. June, Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc. Natl. Acad. Sci. U. S. A. 106, 3360-3365 (2009).
21. Y. Zhao, E. Moon, C. Carpenito, C. M. Paulos, X. Liu, A. L. Brennan, A. Chew, R. G. Carroll, J. Scholler, B. L. Levine, S. M. Albelda, C. H. June, Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor. Cancer Res. 70, 9053-9061 (2010).
22. E. K. Moon, C. Carpenito, J. Sun, L. C. Wang, V. Kapoor, J. Predina, D. J. Powell Jr., J. L. Riley, C. H. June, S. M. Albelda, 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. 17, 4719-4730 (2011).
23. E. L. Servais, C. Colovos, S. S. Kachala, P. S. Adusumilli, Pre-clinical mouse models of primary and metastatic pleural cancers of the lung and breast and the use of bioluminescent imaging to monitor pleural tumor burden. Curr. Protoc. Pharmacol. Chapter 14, Unit14.21 (2011).
24. E. L. Servais, K. Suzuki, C. Colovos, L. Rodriguez, C. Sima, M. Fleisher, V. W. Rusch, M. Sadelain, P. S. Adusumilli, An in vivo platform for tumor biomarker assessment. PLOS One 6, e26722 (2011).
25. Y. Feng, X. Xiao, Z. Zhu, E. Streaker, M. Ho, I. Pastan, D. S. Dimitrov, A novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependent cell-mediated cytotoxicity. Mol. Cancer Ther. 8, 1113-1118 (2009).
26. J. Maher, R. J. Brentjens, G. Gunset, I. Rivière, M. Sadelain, Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzCD28 receptor. Nat. Biotechnol. 20, 70-75 (2002).
27. R. J. Brentjens, E. Santos, Y. Nikhamin, R. Yeh, M. Matsushita, K. La Perle, A. Quintás-Cardama, S. M. Larson, M. Sadelain, Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clin. Cancer Res. 13, 5426-5435 (2007).
28. P. S. Adusumilli, B. M. Stiles, M. K. Chan, M. Mullerad, D. P. Eisenberg, L. Ben-Porat, R. Huq, V. W. Rusch, Y. Fong, Imaging and therapy of malignant pleural mesothelioma using replicationcompetent herpes simplex viruses. J. Gene Med. 8, 603-615 (2006).
29. F. Sallusto, D. Lenig, R. Förster, M. Lipp, A. Lanzavecchia, Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708-712 (1999).
30. E. A. Reits, J. W. Hodge, C. A. Herberts, T. A. Groothuis, M. Chakraborty, E. K. Wansley, K. Camphausen, R. M. Luiten, A. H. De Ru, J. Neijssen, A. Griekspoor, E. Mesman, F. A. Verreck, H. Spits, J. Schlom, P. Van Veelen, J. J. Neefjes, Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J. Exp. Med. 203, 1259-1271 (2006).
31. S. C. Formenti, S. Demaria, Systemic effects of local radiotherapy. Lancet Oncol. 10, 718-726 (2009).
32. D. Zamarin, R. B. Holmgaard, S. K. Subudhi, J. S. Park, M. Mansour, P. Palese, T. Merghoub, J. D. Wolchok, J. P. Allison, Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci. Transl. Med. 6, 226ra232 (2014).
33. T. Kitahara, O. Watanabe, A. Yamaura, H. Makino, T. Watanabe, G. Suzuki, K. Okumura, Establishment of interleukin 2 dependent cytotoxic T lymphocyte cell line specific for autologous brain tumor and its intracranial administration for therapy of the tumor. J. Neurooncol. 4, 329-336 (1987).
34. E. R. Sigurdson, J. A. Ridge, N. Kemeny, J. M. Daly, Tumor and liver drug uptake following hepatic artery and portal vein infusion. J. Clin. Oncol. 5, 1836-1840 (1987).
35. A. K. Thom, H. R. Alexander, M. P. Andrich, W. C. Barker, S. A. Rosenberg, D. L. Fraker, Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor, interferon gamma, and melphalan. J. Clin. Oncol. 13, 264-273 (1995).
36. J. Tchou, L. C. Wang, B. Selven, H. Zhang, J. Conejo-Garcia, H. Borghaei, M. Kalos, R. H. Vondeheide, S. M. Albelda, C. H. June, P. J. Zhang, Mesothelin, a novel immunotherapy target for triple negative breast cancer. Breast Cancer Res. Treat. 133, 799-804 (2012).
37. F. Kawamata, H. Kamachi, T. Einama, S. Homma, M. Tahara, M. Miyazaki, S. Tanaka, T. Kamiyama, H. Nishihara, A. Taketomi, S. Todo, Intracellular localization of mesothelin predicts patient prognosis of extrahepatic bile duct cancer. Int. J. Oncol. 41, 2109-2118 (2012).
38. T. Einama, S. Homma, H. Kamachi, F. Kawamata, K. Takahashi, N. Takahashi, M. Taniguchi, T. Kamiyama, H. Furukawa, Y. Matsuno, S. Tanaka, H. Nishihara, A. Taketomi, S. Todo, Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer. Br. J. Cancer 107, 137-142 (2012).
39. R. Hassan, Z. G. Laszik, M. Lerner, M. Raffeld, R. Postier, D. Brackett, Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis. Am. J. Clin. Pathol. 124, 838-845 (2005).
40. H. F. Frierson Jr., C. A. Moskaluk, S. M. Powell, H. Zhang, L. A. Cerilli, M. H. Stoler, H. Cathro, G. M. Hampton, Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas. Hum. Pathol. 34, 605-609 (2003).
41. P. Argani, C. Iacobuzio-Donahue, B. Ryu, C. Rosty, M. Goggins, R. E. Wilentz, S. R. Murugesan, S. D. Leach, E. Jaffee, C. J. Yeo, J. L. Cameron, S. E. Kern, R. H. Hruban, Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: Identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE). Clin. Cancer Res. 7, 3862-3868 (2001).
42. C. U. Louis, B. Savoldo, G. Dotti, M. Pule, E. Yvon, G. D. Myers, C. Rossig, H. V. Russell, O. Diouf, E. Liu, H. Liu, M. F. Wu, A. P. Gee, Z. Mei, C. M. Rooney, H. E. Heslop, M. K. Brenner, Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 118, 6050-6056 (2011).
43. G. L. Beatty, A. R. Haas, M. V. Maus, D. A. Torigian, M. C. Soulen, G. Plesa, A. Chew, Y. Zhao, B. L. Levine, S. M. Albelda, M. Kalos, C. H. June, Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol. Res. 2, 112-120 (2014).
44. + T cells expressing an MHC class I-restricted TCR of nanomolar affinity. Mol. Ther. 20, 652-660 (2012).
45. + T cells with the ability to recognize and kill tumor cell lines. J. Immunol. 179, 5845-5854 (2007).
46. J. D. Stone, D. H. Aggen, A. Schietinger, H. Schreiber, D. M. Kranz, A sensitivity scale for targeting T cells with chimeric antigen receptors (CARs) and bispecific T-cell Engagers (BiTEs). Oncoimmunology 1, 863-873 (2012).
47. E. Lanitis, M. Poussin, I. S. Hagemann, G. Coukos, R. Sandaltzopoulos, N. Scholler, D. J. Powell Jr., Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor. Mol. Ther. 20, 633-643 (2012).
48. R. Hassan, S. J. Cohen, M. Phillips, I. Pastan, E. Sharon, R. J. Kelly, C. Schweizer, S. Weil, D. Laheru, Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers. Clin. Cancer Res. 16, 6132-6138 (2010).
49. R. Hassan, H. L. Kindler, T. Jahan, L. Bazhenova, M. Reck, A. Thomas, I. Pastan, J. Parno, D. J. O'Shannessy, P. Fatato, J. D. Maltzman, B. A. Wallin, Phase II clinical trial of amatuximab, a chimeric anti-mesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clin. Cancer Res.
50. M. V. Maus, A. R. Haas, G. L. Beatty, S. M. Albelda, B. L. Levine, X. Liu, Y. Zhao, M. Kalos, C. H. June, T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol. Res. 1, 26-31 (2013).
51. A. Di Stasi, S. K. Tey, G. Dotti, Y. Fujita, A. Kennedy-Nasser, C. Martinez, K. Straathof, E. Liu, A. G. Durett, B. Grilley, H. Liu, C. R. Cruz, B. Savoldo, A. P. Gee, J. Schindler, R. A. Krance, H. E. Heslop, D. M. Spencer, C. M. Rooney, M. K. Brenner, Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 365, 1673-1683 (2011).
52. X. Wang, W. C. Chang, C. W. Wong, D. Colcher, M. Sherman, J. R. Ostberg, S. J. Forman, S. R. Riddell, M. C. Jensen, A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 118, 1255-1263 (2011).
53. L. J. Cooper, L. Ausubel, M. Gutierrez, S. Stephan, R. Shakeley, S. Olivares, L. M. Serrano, L. Burton, M. C. Jensen, S. J. Forman, D. L. Di Giusto, Manufacturing of gene-modified cytotoxic T lymphocytes for autologous cellular therapy for lymphoma. Cytotherapy 8, 105-117 (2006).
54. C. C. Kloss, M. Condomines, M. Cartellieri, M. Bachmann, M. Sadelain, Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat. Biotechnol. 31, 71-75 (2013).
55. V. D. Fedorov, M. Sadelain, C. C. Kloss, Novel approaches to enhance the specificity and safety of engineered T cells. Cancer J. 20, 160-165 (2014).
56. V. D. Fedorov, M. Themeli, M. Sadelain, PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci. Transl. Med. 5, 215ra172 (2013).
57. T. P. Gade, W. Hassen, E. Santos, G. Gunset, A. Saudemont, M. C. Gong, R. Brentjens, X. S. Zhong, M. Stephan, J. Stefanski, C. Lyddane, J. R. Osborne, I. M. Buchanan, S. J. Hall, W. D. Heston, I. Rivière, S. M. Larson, J. A. Koutcher, M. Sadelain, Targeted elimination of prostate cancer by genetically directed human T lymphocytes. Cancer Res. 65, 9080-9088 (2005).
58. K. Suzuki, E. L. Servais, N. P. Rizk, S. B. Solomon, C. S. Sima, B. J. Park, S. S. Kachala, M. Zlobinsky, V. W. Rusch, P. S. Adusumilli, Palliation and pleurodesis in malignant pleural effusion: The role for tunneled pleural catheters. J. Thorac. Oncol. 6, 762-767 (2011).
59. C. M. Van Herpen, J. A. Van Der Laak, I. J. De Vries, J. H. Van Krieken, P. C. De Wilde, M. G. Balvers, G. J. Adema, P. H. De Mulder, Intratumoral recombinant human interleukin-12 administration in head and neck squamous cell carcinoma patients modifies locoregional lymph node architecture and induces natural killer cell infiltration in the primary tumor. Clin. Cancer Res. 11, 1899-1909 (2005).
60. S. G. Carpenter, J. Carson, Y. Fong, Regional liver therapy using oncolytic virus to target hepatic colorectal metastases. Semin. Oncol. 37, 160-169 (2010).
61. D. Hollyman, J. Stefanski, M. Przybylowski, S. Bartido, O. Borquez-Ojeda, C. Taylor, R. Yeh, V. Capacio, M. Olszewska, J. Hosey, M. Sadelain, R. J. Brentjens, I. Rivière, Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy. J. Immunother. 32, 169-180 (2009).
62. J. L. McCoy, R. B. Herberman, E. B. Rosenberg, F. C. Donnelly, P. H. Levine, C. Alford, 51 Chromium-release assay for cell-mediated cytotoxicity of human leukemia and lymphoid tissue-culture cells. Natl. Cancer Inst. Monogr. 37, 59-67 (1973).
63. P. S. Adusumilli, D. P. Eisenberg, B. M. Stiles, S. Chung, M. K. Chan, V. W. Rusch, Y. Fong, Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus. J. Thorac. Cardiovasc. Surg. 132, 1179-1188 (2006).
64. B. M. Stiles, P. S. Adusumilli, A. Bhargava, S. F. Stanziale, T. H. Kim, M. K. Chan, R. Huq, R. Wong, V. W. Rusch, Y. Fong, Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer. Cancer Gene Ther. 13, 53-64 (2006).
65. B. A. Rabinovich, Y. Ye, T. Etto, J. Q. Chen, H. I. Levitsky, W. W. Overwijk, L. J. Cooper, J. Gelovani, P. Hwu, Visualizing fewer than 10 mouse T cells with an enhanced firefly luciferase in immunocompetent mouse models of cancer. Proc. Natl. Acad. Sci. U. S. A. 105, 14342-14346 (2008).
66. I. K. Na, J. C. Markley, J. J. Tsai, N. L. Yim, B. J. Beattie, A. D. Klose, A. M. Holland, A. Ghosh, U. K. Rao, M. T. Stephan, I. Serganova, E. B. Santos, R. J. Brentjens, R. G. Blasberg, M. Sadelain, M. R. Van Den Brink, Concurrent visualization of trafficking, expansion, and activation of T lymphocytes and T-cell precursors in vivo. Blood 116, e18-e25 (2010).