Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 7/2008

01.07.2008 | Original Article

RETRACTED ARTICLE: Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF

verfasst von: Nobuto Yamamoto, Hirofumi Suyama, Hiroaki Nakazato, Nobuyuki Yamamoto, Yoshihiko Koga

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2008

Einloggen, um Zugang zu erhalten

Abstract

Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent macrophage-activating factor (GcMAF) ever discovered, but it produces no side effect in humans. Macrophages treated with GcMAF (100 pg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of GcMAF therapy. After 32–50 weekly administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.
Literatur
1.
Zurück zum Zitat Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 172:248–254CrossRef Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 172:248–254CrossRef
2.
Zurück zum Zitat Braun S, Pantel K (1999) Micrometastatic bone marrows involvement detection and prognostic significance. Med Oncol 16:154–165PubMedCrossRef Braun S, Pantel K (1999) Micrometastatic bone marrows involvement detection and prognostic significance. Med Oncol 16:154–165PubMedCrossRef
3.
Zurück zum Zitat Cohen AM, Shank B, Friedman MA (1989) Colorectal cancer. In: Devita VT Jr, Hellman S, Rosenberg SA (eds) Cancer, principle and practice of oncology, 3rd edn. J.B. Lippincott, Philadelphia, pp 895–964 Cohen AM, Shank B, Friedman MA (1989) Colorectal cancer. In: Devita VT Jr, Hellman S, Rosenberg SA (eds) Cancer, principle and practice of oncology, 3rd edn. J.B. Lippincott, Philadelphia, pp 895–964
4.
Zurück zum Zitat DeCosse JJ, Tsioulias GJ, Jacobson JS (1994) Colorectal cancer: detection, treatment and rehabilitation. CA Cancer J Clin 44:27–42PubMedCrossRef DeCosse JJ, Tsioulias GJ, Jacobson JS (1994) Colorectal cancer: detection, treatment and rehabilitation. CA Cancer J Clin 44:27–42PubMedCrossRef
5.
Zurück zum Zitat Gleason DF (1977) The Veteran,s Administration Cooperative Urological Research Group: histological grading and clinical staging of prostate carcinoma. In: Tannenbaum M (ed) Urologic pathology: the prostate. Lea and Febiger, Philadelphia pp 171–198 Gleason DF (1977) The Veteran,s Administration Cooperative Urological Research Group: histological grading and clinical staging of prostate carcinoma. In: Tannenbaum M (ed) Urologic pathology: the prostate. Lea and Febiger, Philadelphia pp 171–198
6.
Zurück zum Zitat Gold P, Freedman SQ (1965) Demonstration of tumor specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med 121:439–462PubMedCrossRefPubMedCentral Gold P, Freedman SQ (1965) Demonstration of tumor specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med 121:439–462PubMedCrossRefPubMedCentral
7.
Zurück zum Zitat Homma S, Yamamoto N (1990) Activation process of macrophages after in vitro treatment of mouse lymphocytes with dodecylglycerol. Clin Exp Immunol 79:307–313PubMedCrossRefPubMedCentral Homma S, Yamamoto N (1990) Activation process of macrophages after in vitro treatment of mouse lymphocytes with dodecylglycerol. Clin Exp Immunol 79:307–313PubMedCrossRefPubMedCentral
8.
Zurück zum Zitat Homma S, Yamamoto M, Yamamoto N (1993) Vitamin D binding protein (group-specific component, Gc) is the sole serum protein required for macrophage activation after treatment of peritoneal cells with lysophosphatidylcholine. Immunol Cell Biol 71:249–257PubMedCrossRef Homma S, Yamamoto M, Yamamoto N (1993) Vitamin D binding protein (group-specific component, Gc) is the sole serum protein required for macrophage activation after treatment of peritoneal cells with lysophosphatidylcholine. Immunol Cell Biol 71:249–257PubMedCrossRef
9.
Zurück zum Zitat Kanda S, Mochizuki Y, Miyata Y, Kanetake H, Yamamoto N (2002) Vitamin D-binding protein-derived macrophage activating factor, GcMAF, has an antiangiogenic activity both in vivo and in vitro. J Natl Cancer Inst 94:1311–1319PubMedCrossRef Kanda S, Mochizuki Y, Miyata Y, Kanetake H, Yamamoto N (2002) Vitamin D-binding protein-derived macrophage activating factor, GcMAF, has an antiangiogenic activity both in vivo and in vitro. J Natl Cancer Inst 94:1311–1319PubMedCrossRef
10.
Zurück zum Zitat Kisker O, Onizuka S, Becker CM, Fannon M, Flynn E, D’Amato R, Zetter B, Folkman J, Ray R, Swamy N, Pirie-Shepherd S (2003) Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice. Neoplasia 5:32–40PubMedCrossRefPubMedCentral Kisker O, Onizuka S, Becker CM, Fannon M, Flynn E, D’Amato R, Zetter B, Folkman J, Ray R, Swamy N, Pirie-Shepherd S (2003) Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice. Neoplasia 5:32–40PubMedCrossRefPubMedCentral
11.
Zurück zum Zitat Koga Y, Naraparaju VR, Yamamoto N (1999) Antitumor effects of vitamin D3-binding protein-derived macrophage activating factor on Ehrlich tumor bearing mice. Proc Soc Exp Biol Med 220:20–26PubMedCrossRef Koga Y, Naraparaju VR, Yamamoto N (1999) Antitumor effects of vitamin D3-binding protein-derived macrophage activating factor on Ehrlich tumor bearing mice. Proc Soc Exp Biol Med 220:20–26PubMedCrossRef
12.
Zurück zum Zitat Koprowski H, Herlyn M, Steplewski Z, Sears HF (1981) Specific antigen in serum of patients with colon carcinoma. Science 212:53–55PubMedCrossRef Koprowski H, Herlyn M, Steplewski Z, Sears HF (1981) Specific antigen in serum of patients with colon carcinoma. Science 212:53–55PubMedCrossRef
13.
Zurück zum Zitat Link RP, Perlman KL, Pierce EA, Schnoes HK, DeLuca HF (1986) Purification of human serum vitamin D-binding protein by 25-hydroxyvitamin D3-Sepharose chromatography. Anal Biochem 157:262–269PubMedCrossRef Link RP, Perlman KL, Pierce EA, Schnoes HK, DeLuca HF (1986) Purification of human serum vitamin D-binding protein by 25-hydroxyvitamin D3-Sepharose chromatography. Anal Biochem 157:262–269PubMedCrossRef
14.
Zurück zum Zitat Maehara Y, Kohnoe S, Sugimachi K (1990) Chemosensitivity test for carcinoma of digestive organs. Semin Surg Oncol 6:42–47PubMedCrossRef Maehara Y, Kohnoe S, Sugimachi K (1990) Chemosensitivity test for carcinoma of digestive organs. Semin Surg Oncol 6:42–47PubMedCrossRef
15.
Zurück zum Zitat Morton D, Eibler FR, Malmgren RA, Wood WC (1970) Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery 68:158-164PubMed Morton D, Eibler FR, Malmgren RA, Wood WC (1970) Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery 68:158-164PubMed
16.
Zurück zum Zitat Naraparaju VR, Yamamoto N (1994) Roles of ß-galactosidase of B lymphocytes and sialidase of T lymphocytes in inflammation-primed activation of macrophages. Immunol Lett 43:143–148PubMedCrossRef Naraparaju VR, Yamamoto N (1994) Roles of ß-galactosidase of B lymphocytes and sialidase of T lymphocytes in inflammation-primed activation of macrophages. Immunol Lett 43:143–148PubMedCrossRef
17.
Zurück zum Zitat Ngwenya BZ, Yamamoto N (1985) Activation of peritoneal macrophages by lysophosphatidylcholine. Biochim Biophys Acta 839:9-15PubMedCrossRef Ngwenya BZ, Yamamoto N (1985) Activation of peritoneal macrophages by lysophosphatidylcholine. Biochim Biophys Acta 839:9-15PubMedCrossRef
18.
Zurück zum Zitat Ngwenya BZ, Yamamoto N (1986) Effects of inflammation products on immune systems: lysophosphatidylcholine stimulates macrophages. Cancer Immunol Immunother 21:174–182PubMedCrossRef Ngwenya BZ, Yamamoto N (1986) Effects of inflammation products on immune systems: lysophosphatidylcholine stimulates macrophages. Cancer Immunol Immunother 21:174–182PubMedCrossRef
19.
Zurück zum Zitat Ngwenya BZ, Yamamoto N (1990) Contribution of lysophosphatidylcholine treated nonadherent cells to mechanism of macrophage activation. Proc Soc Exp Biol Med 193:118–124PubMedCrossRef Ngwenya BZ, Yamamoto N (1990) Contribution of lysophosphatidylcholine treated nonadherent cells to mechanism of macrophage activation. Proc Soc Exp Biol Med 193:118–124PubMedCrossRef
20.
Zurück zum Zitat Olson RM, Perencevich NP, Malcolm AW, Chaffey JT, Wilson RE (1980) Pattern of recurrence following curative resection of adenocarinoma of the colon and rectum. Cancer 45:2969–2974PubMedCrossRef Olson RM, Perencevich NP, Malcolm AW, Chaffey JT, Wilson RE (1980) Pattern of recurrence following curative resection of adenocarinoma of the colon and rectum. Cancer 45:2969–2974PubMedCrossRef
21.
Zurück zum Zitat Rich T, Gunderson LL, Lew R, Galdibini JJ, Cohen AM, Donaldson G (1983) Patterns of recurrence of rectal cancer after potentially curative surgery. Cancer 52:1317–1329PubMedCrossRef Rich T, Gunderson LL, Lew R, Galdibini JJ, Cohen AM, Donaldson G (1983) Patterns of recurrence of rectal cancer after potentially curative surgery. Cancer 52:1317–1329PubMedCrossRef
22.
Zurück zum Zitat Yamamoto N, Ngwenya BZ (1987) Activation of macrophages by lysophospholipids, and ether derivatives of neutral lipids and phospholipids. Cancer Res 47:2008-2013PubMed Yamamoto N, Ngwenya BZ (1987) Activation of macrophages by lysophospholipids, and ether derivatives of neutral lipids and phospholipids. Cancer Res 47:2008-2013PubMed
23.
Zurück zum Zitat Yamamoto N, Ngwenya BZ, Pieringer PA (1987) Activation of macrophages by ether analogues of lysophospholipids. Cancer Immunol Immunother 25:185–192PubMedCrossRef Yamamoto N, Ngwenya BZ, Pieringer PA (1987) Activation of macrophages by ether analogues of lysophospholipids. Cancer Immunol Immunother 25:185–192PubMedCrossRef
24.
Zurück zum Zitat Yamamoto N, St. Claire DA, Homma S, Ngwenya BZ (1988) Activation of mouse macrophages by alkylglycerols, inflammation products of cancerous tissues. Cancer Res 48:6044–6049PubMed Yamamoto N, St. Claire DA, Homma S, Ngwenya BZ (1988) Activation of mouse macrophages by alkylglycerols, inflammation products of cancerous tissues. Cancer Res 48:6044–6049PubMed
25.
Zurück zum Zitat Yamamoto N, Homma S (1991) Vitamin D3 binding protein (group-specific component, Gc) is a precursor for the macrophage activating signal from lysophosphatidylcholine-treated lymphocytes. Proc Natl Acad Sci USA 88:8539–8543PubMedCrossRefPubMedCentral Yamamoto N, Homma S (1991) Vitamin D3 binding protein (group-specific component, Gc) is a precursor for the macrophage activating signal from lysophosphatidylcholine-treated lymphocytes. Proc Natl Acad Sci USA 88:8539–8543PubMedCrossRefPubMedCentral
26.
Zurück zum Zitat Yamamoto N, Homma S, Haddad JG, Kowalski MN (1991) Vitamin D3 binding protein required for in vitro activation of macrophages after dodecylglycerol treatment of mouse peritoneal cells. Immunol 74:420–424 Yamamoto N, Homma S, Haddad JG, Kowalski MN (1991) Vitamin D3 binding protein required for in vitro activation of macrophages after dodecylglycerol treatment of mouse peritoneal cells. Immunol 74:420–424
27.
Zurück zum Zitat Yamamoto N, Homma S, Millman I (1991) Identification of the serum factor required for in vitro activation of macrophages: role of vitamin D binding protein (group-specific component, Gc) in lysophospholipid activation of mouse peritoneal macrophages. J Immunol 147:273–280PubMed Yamamoto N, Homma S, Millman I (1991) Identification of the serum factor required for in vitro activation of macrophages: role of vitamin D binding protein (group-specific component, Gc) in lysophospholipid activation of mouse peritoneal macrophages. J Immunol 147:273–280PubMed
28.
Zurück zum Zitat Yamamoto N (1993) In vitro enzymatic conversion of glycosylated human vitamin D binding protein to a potent macrophage activating factor. US Patent number: 5,177,002 Yamamoto N (1993) In vitro enzymatic conversion of glycosylated human vitamin D binding protein to a potent macrophage activating factor. US Patent number: 5,177,002
29.
Zurück zum Zitat Yamamoto N, Kumashiro R (1993) Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of ß-galactosidase of B cells and sialidase of T cells. J Immunol 151:2794–2902PubMed Yamamoto N, Kumashiro R (1993) Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of ß-galactosidase of B cells and sialidase of T cells. J Immunol 151:2794–2902PubMed
30.
Zurück zum Zitat Yamamoto N, Kumashiro R, Yamamoto M, Willett NP, Lindsay DD (1993) Regulation of inflammation-primed activation of macrophages by two serum factors, vitamin D3-binding protein and albumin. Infect Immun 61:5388–5891PubMedPubMedCentral Yamamoto N, Kumashiro R, Yamamoto M, Willett NP, Lindsay DD (1993) Regulation of inflammation-primed activation of macrophages by two serum factors, vitamin D3-binding protein and albumin. Infect Immun 61:5388–5891PubMedPubMedCentral
31.
Zurück zum Zitat Yamamoto N (1994) Macrophage activating factor from vitamin D binding protein. US Patent Number: 5,326,749 Yamamoto N (1994) Macrophage activating factor from vitamin D binding protein. US Patent Number: 5,326,749
32.
Zurück zum Zitat Yamamoto N, Naraparaju VR, Srinivasula SM (1995) Structural modification of serum vitamin D3-binding protein and immunosuppression in HIV-infected patients. AIDS Res Human Retrovirus 11:1373–1378CrossRef Yamamoto N, Naraparaju VR, Srinivasula SM (1995) Structural modification of serum vitamin D3-binding protein and immunosuppression in HIV-infected patients. AIDS Res Human Retrovirus 11:1373–1378CrossRef
33.
Zurück zum Zitat Yamamoto N (1996) Structural definition of a potent macrophage activating factor derived from vitamin D3 binding protein with adjuvant activity for antibody production. Mol Immunol 33:1157–1164PubMedCrossRef Yamamoto N (1996) Structural definition of a potent macrophage activating factor derived from vitamin D3 binding protein with adjuvant activity for antibody production. Mol Immunol 33:1157–1164PubMedCrossRef
34.
Zurück zum Zitat Yamamoto N, Naraparaju VR, Asbell SO (1996) Deglycosylation of serum vitamin D-binding protein and immunosuppression in cancer patients. Cancer Res 56:2827–2831PubMed Yamamoto N, Naraparaju VR, Asbell SO (1996) Deglycosylation of serum vitamin D-binding protein and immunosuppression in cancer patients. Cancer Res 56:2827–2831PubMed
35.
Zurück zum Zitat Yamamoto N (1997) Diagnostic and prognostic indices for cancer and AIDS. US Patent Number: 5,620,846 Yamamoto N (1997) Diagnostic and prognostic indices for cancer and AIDS. US Patent Number: 5,620,846
36.
Zurück zum Zitat Yamamoto N, Naraparaju VR (1997) Immunotherapy of BALB/c mice bearing Ehrlich ascites tumor with vitamin D-binding protein-derived macrophage activating factor. Cancer Res 57:2187–2191PubMed Yamamoto N, Naraparaju VR (1997) Immunotherapy of BALB/c mice bearing Ehrlich ascites tumor with vitamin D-binding protein-derived macrophage activating factor. Cancer Res 57:2187–2191PubMed
37.
Zurück zum Zitat Yamamoto N, Naraparaju VR, Urade M (1997) Prognostic utility of serum a-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients. Cancer Res 57:295–299PubMed Yamamoto N, Naraparaju VR, Urade M (1997) Prognostic utility of serum a-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients. Cancer Res 57:295–299PubMed
38.
Zurück zum Zitat Yamamoto N (1998) Vitamin D and the immune system. In: Delves PJ, Roitt I (eds) Encyclopedia of immunology, 2nd edn. Academic, London, pp 2494–2499CrossRef Yamamoto N (1998) Vitamin D and the immune system. In: Delves PJ, Roitt I (eds) Encyclopedia of immunology, 2nd edn. Academic, London, pp 2494–2499CrossRef
39.
Zurück zum Zitat Yamamoto N (1998) Diagnostic and prognostic ELISA assays of serum or plasma a-N-acetylgalactosaminidase for cancer. US Patent number: 5,712,104 Yamamoto N (1998) Diagnostic and prognostic ELISA assays of serum or plasma a-N-acetylgalactosaminidase for cancer. US Patent number: 5,712,104
40.
Zurück zum Zitat Yamamoto N, Naraparaju VR (1998) Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization. Immunol Cell Biol 76:237–244PubMedCrossRef Yamamoto N, Naraparaju VR (1998) Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization. Immunol Cell Biol 76:237–244PubMedCrossRef
41.
Zurück zum Zitat Yamamoto N (2002) Preparation of potent macrophage activating factors derived from cloned vitamin D binding protein and its domain and their therapeutic usage for cancer, HIV-infection and osteopetrosis. US Patent no. 6,410,269 Yamamoto N (2002) Preparation of potent macrophage activating factors derived from cloned vitamin D binding protein and its domain and their therapeutic usage for cancer, HIV-infection and osteopetrosis. US Patent no. 6,410,269
42.
Zurück zum Zitat Yamamoto N, Ueda M (2004) Eradication of HIV by treatment of HIV-infected/AIDS patients with vitamin D-binding protein (Gc protein)-derived macrophage activating factor (GcMAF). Immunology 2000. Medmond Ltd, Bolonia, pp 197–200 Yamamoto N, Ueda M (2004) Eradication of HIV by treatment of HIV-infected/AIDS patients with vitamin D-binding protein (Gc protein)-derived macrophage activating factor (GcMAF). Immunology 2000. Medmond Ltd, Bolonia, pp 197–200
43.
Zurück zum Zitat Yamamoto N, Ueda M (2004) Therapeutic efficacy of vitamin D-binding protein (Gc protein)-derived macrophage activating factor (GcMAF) for prostate and breast cancers. Immunology 2000. Medmond Ltd, Bolonia, pp 201–204 Yamamoto N, Ueda M (2004) Therapeutic efficacy of vitamin D-binding protein (Gc protein)-derived macrophage activating factor (GcMAF) for prostate and breast cancers. Immunology 2000. Medmond Ltd, Bolonia, pp 201–204
44.
Zurück zum Zitat Yamamoto N, Urade M (2005) Pathogenic significance of a-N-acetylgalactosaminidase found in the hemagglutinin of influenza virus. Microbes Infect 7:674–681PubMedCrossRef Yamamoto N, Urade M (2005) Pathogenic significance of a-N-acetylgalactosaminidase found in the hemagglutinin of influenza virus. Microbes Infect 7:674–681PubMedCrossRef
45.
Zurück zum Zitat Yamamoto N (2006) Pathogenic significance of a-N-acetylgalactosaminidase found in the envelope glycoprotein gp160 of human immunodeficiency virus type 1. AIDS Res Human Retrovirus 22:262–271CrossRef Yamamoto N (2006) Pathogenic significance of a-N-acetylgalactosaminidase found in the envelope glycoprotein gp160 of human immunodeficiency virus type 1. AIDS Res Human Retrovirus 22:262–271CrossRef
46.
Zurück zum Zitat Yamamoto N, Suyama H, Yamamoto N-Y, Ushijima N (2008) Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF). Int J Cancer 122:461–467PubMedCrossRef Yamamoto N, Suyama H, Yamamoto N-Y, Ushijima N (2008) Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF). Int J Cancer 122:461–467PubMedCrossRef
47.
Zurück zum Zitat Zbar B, Tanaka T (1971) Immunotherapy of cancer: regression of tumors after intralesional injection of living Mycobacterium bovis. Science 172:271-273PubMedCrossRef Zbar B, Tanaka T (1971) Immunotherapy of cancer: regression of tumors after intralesional injection of living Mycobacterium bovis. Science 172:271-273PubMedCrossRef
48.
Zurück zum Zitat Zhang S, Zhang HS, Cordon-Cardo C, Ragupathi G, Livingston PO (1998) Selection of tumor antigens as targets for immune attack using immunohistochemistry. III. Protein antigen. Clin Cancer Res 4:2669–2676PubMed Zhang S, Zhang HS, Cordon-Cardo C, Ragupathi G, Livingston PO (1998) Selection of tumor antigens as targets for immune attack using immunohistochemistry. III. Protein antigen. Clin Cancer Res 4:2669–2676PubMed
Metadaten
Titel
RETRACTED ARTICLE: Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF
verfasst von
Nobuto Yamamoto
Hirofumi Suyama
Hiroaki Nakazato
Nobuyuki Yamamoto
Yoshihiko Koga
Publikationsdatum
01.07.2008
Verlag
Springer-Verlag
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 7/2008
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-007-0431-z

Weitere Artikel der Ausgabe 7/2008

Cancer Immunology, Immunotherapy 7/2008 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.