INTRODUCTION

Cancer vaccines have been a goal of medical research for many years. Lately, several studies have explored the autologous vaccination model in order to consider the antigenic individuality of malignant tumors. In this area of research, some experimental and clinical studies have obtained promising results. The results of melanoma treated with a vaccine manufactured with autologous hapten-modified tumor cells and adjuvant BCG1 and the results of renal-cell carcinoma, pancreatic cancer, and other solid tumors treated with a vaccine prepared from heat-shock proteins (HSP) from autologous tumors2-5 are examples. However, the favorable results reported were temporary in every case. Tumor escape mechanisms from immunological control include changes in malignant cell antigens due to a high rate of spontaneous mutations associated with their rapid proliferative rate, as well as environmental conditions including chemotherapy and the host biological response.6 Most autologous vaccines have been obtained from surgical tumor specimens. These vaccines, when successful, generated an immune response that recognized and controlled tumor cells with the antigen endowment present in the cells from which the vaccine was obtained. However, if the antigenic library of the tumor cells changes, immune mechanisms will be unable to recognize and control the malignant disease, thus resulting in clinical progression. It is not possible to update these vaccines for each and every new antigenic profile of tumor cells because it is not feasible to obtain new surgical specimens frequently. In order to obtain a series of autologous vaccines using frequently updated tumor antigens, we explored autologous blood as an immunogen source in cancer patients. In 1995, we reported the antitumoral effect of an autologous blood protein fraction that was inoculated repeatedly in cancer patients.7,8 This paper reports the procedure used to obtain an autologous blood fraction with immunogenic properties from cancer patients. The procedure can be performed repeatedly.

  1. Berd D, Kairys J, Dunton Ch, Mastrangelo MJ, Sato T, Maguire H (1998) Autologous, Hapten-Modified Vaccine as a Treatment for Human Cancers. Seminars in Oncology 1998; 25:646.

  2. Amato RJ, Wood LS, Savary Ch, Wood Ch, Hawkins EA, Reitsma DG, Srivastava P (1999) Patients with Renal Cell Carcinoma (RCC) Using Autologous Tumor-Derived Heat Shock Protein-Peptide Complex (HSPPC-96) With or Without Interleukin-2 (IL-2). 35th Annual meeting of the ASCO, May.

  3. Menoret A, Bell G. Purification of multiple heat shock proteins from a single tumor sample. J Immunology Methods 2000; 237:119.

  4. Janetzki S, Palla D, Rosenhauer V, Lochs H, Lewis, JJ, Srivastava PK. Immunization of cancer patients with autologous cancer-derived Heat shock protein gp96 preparations: A pilot study. Int J Cancer 2000; 88:232.

  5. Lewis JJ, Janetzki S, Livingston PhO, Desantis D, Williams L, Klimstra D, et al. Pilot Trial of Vaccination with Autologous Tumor-Derived gp96 Heat Shock Protein-Peptide Complex (HSPPC-96) in Patients with Resected Pancreatic Adenocarcinoma. 35th Annual meeting of the ASCO, May, 1999.

  6. Chan AD, Morton DL (1998) Active Immunotherapy With Allogeneic Tumor Cell Vaccines: Present Status. Seminars in Oncology 1998; 25:611.

  7. Lasalvia E, Cucchi S, DeStefani E, Deneo H, Fierro L, Mechoso B, et al. Inducción autóloga de fibrogénesis tumoral (Autologous Induction of tumor fibrogenesis). Neoplasia (Spain) 1995; 1:5.

  8. Lasalvia E, Cucchi S, Carlevaro T, Vázquez J, Riotorto R, Fierro L. Anti-metastatic effect of a blood fraction from cancer patients. 31st Annual meeting of the ASCO, May 1995: A730.


Historically, the effect of vaccines -particularly against pathogens- has been assessed by measurement of their induction of a B-cell-mediated -or humoral- immune response, i.e. the production of pathogen-specific antibodies. In the study of both infectious diseases and cancer, a majority of potential immune targets are only expressed intra-cellularly, and are thus inaccessible to antibody-mediated elimination. T-cell mediated immunity, by contrast, has the potential to recognize targets expressed either extra- or intra-cellularly and has therefore been studied extensively for treatment of these diseases.
A number of pre-clinical and clinical studies have demonstrated that vaccines against pathogens, bystander (non-pathogenic) proteins, tumor-associated antigens, or whole tumor cells, can induce specific T-cell mediated immune responses.[1][2][3][4][5][6] A number of approaches have been considered to amplify T cell mediated immune responses(e.g. IL-2, CTLA-4, IL-7, CD137), and some of these have shown clinical efficacy in eliminating particular types of cancer, most notably melanoma and renal cell carcinoma.

1. Neelapu SS, Kwak LW, Kobrin CB, et al. Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma. Nat Med 2005;11(9):986-91.
2. Biagi E, Rousseau R, Yvon E, et al. Responses to human CD40 ligand/human interleukin-2 autologous cell vaccine in patients with B-cell chronic lymphocytic leukemia. Clin Cancer Res 2005;11(19 Pt 1):6916-23.
3. Monsurro V, Nagorsen D, Wang E, et al. Functional heterogeneity of vaccine-induced CD8(+) T cells. J Immunol 2002;168(11):5933-42.
4. Dudley ME, Nishimura MI, Holt AK, Rosenberg SA. Antitumor immunization with a minimal peptide epitope (G9-209-2M) leads to a functionally heterogeneous CTL response. J Immunother 1999;22(4):288-98.
5. Berd D, Sato T, Cohn H, Maguire HC, Jr., Mastrangelo MJ. Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases. Int J Cancer 2001;94(4):531-9.
6. Rousseau RF, Biagi E, Dutour A, et al. Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. Blood 2006;107(4):1332-41.

Photo Dynamic Therapy and vaccines:

Cancer Res. 2002 Mar 15;62(6):1604-8.
Generation of effective antitumor vaccines using photodynamic therapy.
Gollnick SO, Vaughan L, Henderson BW.

PDT Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. Sandra.Gollnick@roswellpark.org
Abstract
Preclinical studies have shown that photodynamic therapy (PDT) of tumors augments the host antitumor immune response. However, the role of the PDT effect on tumor cells as opposed to the host tissues has not been determined. To test the contribution of the direct effects of PDT on tumor cells to the enhanced antitumor response by the host, we examined the immunogenicity of PDT-generated murine tumor cell lysates in a preclinical vaccine model. We found that the PDT-generated tumor cell lysates were potent vaccines and that PDT-generated vaccines are more effective than other modes of creating whole tumor vaccines, i.e., UV or ionizing irradiation, and unlike other traditional vaccines, PDT vaccines do not require coadministration of an adjuvant to be effective. PDT vaccines are tumor specific and appear to induce a cytotoxic T-cell response. We have demonstrated that although both UV and PDT-generated tumor cell lysates are able to induce phenotypic DC maturation, only PDT-generated lysates are able to activate DCs to express IL-12, which is critical to the development of a cellular immune response. Our results show that PDT effects on tumor cells alone are sufficient to generate an antitumor immune response, indicating that the direct tumor effects of PDT play an important role in enhancing that host antitumor immune response. These studies also suggest that in addition to the role of PDT as a therapeutic modality, PDT-generated vaccines may have clinical potential as an adjuvant therapy.

PMID: 11912128 [PubMed - indexed for MEDLINE]Free Article

 

Vaccine paper: Lasilviaprisco