The preparation of anticancer vaccine for patients with multiple myeloma on the base of monoclonal immunoglobulin loaded dendritic cells

Česká verze

Authors: D. Očadlíková ^1,2; L. Zahradová ^2,3; L. Kovářová ^1,2; J. Smejkalová ^1,2; L. Pour ^2,3; P. Vidláková ^1,2; D. Kyjovská ¹; J. Moravcová ¹; M. Rycová ¹; H. Novotná ⁴; I. Jelínková ⁵; M. Penka ¹; J. Michálek ²; R. Hájek ^1,2,3
Authors place of work: Laboratoř experimentální hematologie a buněčné imunoterapie, Oddělení klinické hematologie, FN Brno 2Univerzitní centrum buněčné imunoterapie a Česká myelomová skupina – Univerzitní výzkumné centrum, MU Brno 3Interní hematoonkologická klinika, FN Brno 4Od ¹
Published in the journal: Klin Onkol 2009; 22(2): 67-72
Category: Původní práce

Summary

Backgrounds:
On June 2006, phase II clinical trial focused on anticancer vaccination of multiple myeloma patients, was started. On September 2007, the immune and clinical response evaluation of first four patients was finished. The anticancer vaccine contained dendritic cells loaded with monoclonal immunoglobulin produced by myeloma cells.

Methods and Patients:
Within the frame of phase II clinical trial were vaccinated four myeloma patients with stable disease. It was administered six vaccines for each patient, monthly. The dendritic cells were cultured from the patient’s peripheral blood mononuclear cells and loaded with autologous monoclonal immunoglobulin under the good manufacturing practice conditions. After the safety and quality control, the satisfactory vaccine was administered to the patient. The functional characteristic of dendritic cells was evaluated using flow cytometry, the immune response was evaluated using ELISpot. The clinical response was monitored using monoclonal immunoglobulin concentration in patient’s sera.

Results and Conclusion:
The immune response detected using ELISpot was observed in 3/4 patients. The monoclonal immunoglobulin concentration was changeable for all twelve months, but never exceeded the range of 25% for minimal clinical response achievement. During the vaccination, no significant toxicities or negative side-effects were observed. The clinical trial is going on with vaccination other patients with multiple myeloma.

Key words:
multiple myeloma – cancer vaccines – dendritic cells

Zdroje

1. Österborg A, Yi Q, Bergenbrant S et al. Idiotype immunization combined with granulocyte-macrophage colony-stimulating factor in myeloma patients induced type I, major histocompatibility complex-restricted, CD8- and CD4-specific T-cell responses. Blood 1998; 91: 2459–2466.

2. Titzer S, Christensen O, Bohlen H et al. Vaccination of multiple myeloma patints with idiotype-pulsed dendritic cells. Immunological and clinical aspects. Br J Haematol 2000; 108: 805–816.

3. Brossart P, Wirths S, Kanz L et al. Dendritic cells in cancer vaccines. Exp Hematol 2001; 29: 1247–1255.

4. Büchler T, Hanák L, Smejkalová J et al. Využití monoklonálního imunoglobulinu k přípravě protinádorové vakcíny u nemocných s mnohočetným myelomem – první zkušenosti z klinické studie. Klin Onkol 2004; 17: 64–67.

5. Zahradová L, Büchler T, Hájek Ret al. Protinádorová vakcína s využitím monoklonálního imunoglobulinu u nemocných s mnohočetným myelomem – výsledky klinické studie fáze II. Klin Onkol 2006; 1: 26–29.

6. Reichardt V, Okada CY, Levy R et al. Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma-a feasibility study. Blood 1999; 93: 2411–2419.

7. Massaia M, Borrione P, Battaglio S et al. Idiotype vaccination in human myeloma: generation of tumor-specific immune responses after high dose chemotherapy. Blood 1999; 94: 673–683.

8. Kwak LW, Taub DD, Bryant EM et al. Transfer of myeloma idiotype-specific immunity from an actively immunised marrow donor. Lancet 1995; 345: 1016–1020.

9. Friberger P, Knos M, Mellstam L. Endotoxin and their detection with the Limulus Amebocyte Lysate Test. New York: Alan R. Liss 1982: 195–206.

10. Očadlíková D, Kovářová L, Michálek J et al. Identifikace myelom-specifických T lymfocytů na základě produkce interferonu gama. Edukační sborník XXVIII. brněnské onkologické dny a XVIII. konference pro sestry a laboranty 26.–28.května 2004; 53: 113–116.

11. Zhou LJ, Tedder TF. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J Immunol 1995; 154: 3821–3835.

12. Schulze J, Nadler LM, Gribben JG. B7-mediated costimulation and the immune response. Blood Rev 1996; 10: 111–127.

13. Blade J, Samson D, Reece D et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high dose therapy and haemopoietic stem cell transplantation. Br J Haematol 1998; 102: 1115–1123.

14. Bergenbrant S, Yi Q, Osterborg A et al. Modulation of anti idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients. Br J Haematol 1996; 92: 840–846.

15. Titzer S, Christensen O, Bohlen H et al. Vaccination of multiple myeloma patients with idiotype-pulsed dendritic cells: immunological and clinical aspects. Br J Haematol 2000; 108: 805–816.

16. Yi Q, Desikan R, Munshi N et al. Optimizing dendritic cell based immunotherapy in multiple myeloma. Br J Haematol 2002; 117: 297–305.

17. Ridgway D. The first 1000 dendritic cells vaccines. Cancer Invest 2003; 21: 873–886.

18. Zeis M, Frenzke H, Steinmann J et al. Dendritic cells pulsed with idiotypic determinants induce anti tumor immunity against established multiple myeloma. Blood 1998; 92: 4229–4237.