Immunization of NSCLC Patients with Antigen-pulsed Immature Autologous Dendritic Cells

Overview

Journal Lung Cancer

Specialty Oncology

Date 2007 May 19

PMID 17509725

Citations 32

Authors

Edward A Hirschowitz

Terry Foody

Giovanna E Hidalgo

John R Yannelli

Affiliations

Soon will be listed here.

Abstract

Only a handful of NSCLC patients have been included in dendritic cell (DC) vaccine clinical trials. We had previously reported a series of 16 individuals with stages IA-IIIB NSCLC who received autologous DC vaccines matured with dendritic cell/T cell-derived maturation factor (DCTCMF). Here we report the results of a continuation study with similar inclusion criteria, immunization protocol, and analysis, using an immature DC vaccine. Of the 14 participants, 7 had undergone surgical resection (stage I/II), with or without adjuvant therapy, and 7 with unresectable stage III had been treated with chemo-radiation alone. Autologous DCs were pulsed with apoptotic bodies derived from an allogeneic NSCLC cell line that over-expresses Her2/neu, CEA, WT1, Mage2, and survivin. DCs were not exposed to any maturation stimulus. Individuals received two intradermal vaccines (average 8.1x10(7) DC per immunization) 1 month apart. Immune responses were measured by IFN-gamma ELISPOT, comparing relative number of antigen-reactive T-cells from pre-vaccine to timepoints post-immunization. Immunologic responses were seen in 4/7 stage III unresectable, and 6/7 stage I/II surgically resected patients, including 3/3 resected patients who had also received adjuvant chemo-radiation. There were no related adverse events. One of seven surgically resected patients recurred and 4/7 stage III patients progressed. Three of five patients with progressive disease showed no immunologic response. Data indicate that immature DC pulsed with apoptotic tumour cells have similar biologic activity to a DCTCMF-matured DC preparation delivered in a similar clinical protocol. Therapeutic efficacy is unknown and clinical outcomes are anecdotal.

Citing Articles

Characteristics of tumor microenvironment and novel immunotherapeutic strategies for non-small cell lung cancer.

Wang F, Yang M, Luo W, Zhou Q J Natl Cancer Cent. 2024; 2(4):243-262.

PMID: 39036549 PMC: 11256730. DOI: 10.1016/j.jncc.2022.10.002.

Neoantigen Identification and Dendritic Cell-Based Vaccines for Lung Cancer Immunotherapy.

Kumari K, Singh A, Chaudhary A, Singh R, Shanker A, Kumar V Vaccines (Basel). 2024; 12(5).

PMID: 38793749 PMC: 11125796. DOI: 10.3390/vaccines12050498.

Dendritic Cell Vaccination in Non-Small Cell Lung Cancer: Remodeling the Tumor Immune Microenvironment.

Abascal J, Oh M, Liclican E, Dubinett S, Salehi-Rad R, Liu B Cells. 2023; 12(19).

PMID: 37830618 PMC: 10571973. DOI: 10.3390/cells12192404.

Nanotechnology-Based Nucleic Acid Vaccines for Treatment of Ovarian Cancer.

Gildiz S, Minko T Pharm Res. 2022; 40(1):123-144.

PMID: 36376606 PMC: 9663189. DOI: 10.1007/s11095-022-03434-4.

Dendritic Cell-Based Immunotherapy in Hot and Cold Tumors.

Kang B, Lee H Int J Mol Sci. 2022; 23(13).

PMID: 35806328 PMC: 9266676. DOI: 10.3390/ijms23137325.

References

Hirschowitz E, Hiestand D, Yannelli J . Vaccines for lung cancer. J Thorac Oncol. 2007; 1(1):93-104. View

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon J, Vansteenkiste J . Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004; 350(4):351-60. DOI: 10.1056/NEJMoa031644. View

Adema G, de Vries I, Punt C, Figdor C . Migration of dendritic cell based cancer vaccines: in vivo veritas?. Curr Opin Immunol. 2005; 17(2):170-4. DOI: 10.1016/j.coi.2005.01.004. View

Nestle F, Farkas A, Conrad C . Dendritic-cell-based therapeutic vaccination against cancer. Curr Opin Immunol. 2005; 17(2):163-9. DOI: 10.1016/j.coi.2005.02.003. View

Mocellin S, Mandruzzato S, Bronte V, Lise M, Nitti D . Part I: Vaccines for solid tumours. Lancet Oncol. 2004; 5(11):681-9. DOI: 10.1016/S1470-2045(04)01610-9. View

Kapsenberg M, Hilkens C, Wierenga E, Kalinski P . The paradigm of type 1 and type 2 antigen-presenting cells. Implications for atopic allergy. Clin Exp Allergy. 1999; 29 Suppl 2:33-6. View

Rissoan M, Soumelis V, Kadowaki N, Grouard G, Briere F, de Waal Malefyt R . Reciprocal control of T helper cell and dendritic cell differentiation. Science. 1999; 283(5405):1183-6. DOI: 10.1126/science.283.5405.1183. View

Rovere P, Vallinoto C, Bondanza A, Crosti M, Rescigno M, Ricciardi-Castagnoli P . Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function. J Immunol. 1998; 161(9):4467-71. View

Groux H, Bigler M, De Vries J, Roncarolo M . Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells. J Exp Med. 1996; 184(1):19-29. PMC: 2192687. DOI: 10.1084/jem.184.1.19. View

10.

Godoy-Ramirez K, Franck K, Mahdavifar S, Andersson L, Gaines H . Optimum culture conditions for specific and nonspecific activation of whole blood and PBMC for intracellular cytokine assessment by flow cytometry. J Immunol Methods. 2004; 292(1-2):1-15. DOI: 10.1016/j.jim.2004.04.028. View

11.

Hirschowitz E, Foody T, Kryscio R, Dickson L, Sturgill J, Yannelli J . Autologous dendritic cell vaccines for non-small-cell lung cancer. J Clin Oncol. 2004; 22(14):2808-15. DOI: 10.1200/JCO.2004.01.074. View

12.

Ip W, Lau Y . Distinct maturation of, but not migration between, human monocyte-derived dendritic cells upon ingestion of apoptotic cells of early or late phases. J Immunol. 2004; 173(1):189-96. DOI: 10.4049/jimmunol.173.1.189. View

13.

Cranmer L, Trevor K, Hersh E . Clinical applications of dendritic cell vaccination in the treatment of cancer. Cancer Immunol Immunother. 2003; 53(4):275-306. PMC: 11032969. DOI: 10.1007/s00262-003-0432-5. View

14.

Spira A, Ettinger D . Multidisciplinary management of lung cancer. N Engl J Med. 2004; 350(4):379-92. DOI: 10.1056/NEJMra035536. View

15.

Wroblewski J, Bixby D, Borowski C, Yannelli J . Characterization of human non-small cell lung cancer (NSCLC) cell lines for expression of MHC, co-stimulatory molecules and tumor-associated antigens. Lung Cancer. 2001; 33(2-3):181-94. DOI: 10.1016/s0169-5002(01)00210-0. View

16.

Chen Z, Moyana T, Saxena A, Warrington R, Jia Z, Xiang J . Efficient antitumor immunity derived from maturation of dendritic cells that had phagocytosed apoptotic/necrotic tumor cells. Int J Cancer. 2001; 93(4):539-48. DOI: 10.1002/ijc.1365. View

17.

Jonuleit H, Tuting T, Stuge T, Paragnik L, Kandemir A, Lee P . A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer. 2001; 93(2):243-51. DOI: 10.1002/ijc.1323. View

18.

Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu Y . Immunobiology of dendritic cells. Annu Rev Immunol. 2000; 18:767-811. DOI: 10.1146/annurev.immunol.18.1.767. View

19.

Kalinski P, Hilkens C, Wierenga E, Kapsenberg M . T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol Today. 1999; 20(12):561-7. DOI: 10.1016/s0167-5699(99)01547-9. View

20.

Keilholz U, Weber J, Finke J, Gabrilovich D, Kast W, Disis M . Immunologic monitoring of cancer vaccine therapy: results of a workshop sponsored by the Society for Biological Therapy. J Immunother. 2002; 25(2):97-138. DOI: 10.1097/00002371-200203000-00001. View