Abstract
Active specific immunotherapy (ASI) procedures usually involve active vaccination with intact, but inactivated tumor cells or with tumor-derived subcellular membrane fractions. Such material is modified in various ways to make it more immunogenic. Modified tumor cell vaccines which have been applied in cancer patients were prepared for instance by polymerization of autologous tumor tissue (Tallberg 1974; Tykkä et al. 1974; Tallberg et al. 1986; Tallberg and Tykkä 1986; Tallberg et al. 1987; Kurth et al. 1987; Fowler 1986), by neurami-nidase treatment (Wunderlich et al. 1985), by chemical modification (Skornick et al. 1984), by the admixture of viruses (Cassel et al. 1977, 1983, 1986; Murray et al. 1977; Hersey et al. 1986, 1987; Wallack et al. 1986; Freedman et al. 1983; Sinkovics 1977), bacteria, in particular C. parvum (McCune et al. 1979, 1984), and bacillus Calmette-Guerin (BCG; Mathe et al. 1986; Hoover et al. 1984, 1985), fungi (Schärfe et al. 1986; Fowler 1986), Freun’s adjuvant (Hollinshead 1987), carrier proteins such as Keyhole Limpet hemocyanine (KLH; Klippel et al. 1981) or of biological response modifiers (Cortesina et al. 1988; Forni et al. 1984) as adjuvants. Some concepts of ASI procedures have been developed over years in well-defined animal models. Major contributions to the understanding of the principles of active-specific immunotherapy were made in the line 10 hepatocarcinoma guinea-pig tumor model (Hanna et al. 1979, 1980; Hanna and Key 1982), and in the well-characterized, highly metastatic ESb mouse lymphoma model (Schirrmacher et al. 1979, 1982, 1986; Bosslet et al. 1979; Heicappell et al. 1986). In the guinea-pig model a series of studies demonstrated that BCG, admixed with tumor cells, could induce a degree of systemic tumor immunity that would eliminate a small, disseminated tumor burden when the vaccine was carefully controlled for such variables as the number of viable, but nontumorigenic tumor cells (107 optimal), the ratio of viable BCG organisms to tumor cells (1:1) and the vaccination regimen (3 vaccines, 1 week apart; Hanna et al. 1980). We reported previously on the prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells in the ESb tumor model (Heicappell et al. 1986; Schirrmacher et al. 1986). A nonlytic, avirulent strain of the paramyxovirus Newcastle disease virus (NDV) was used to infect the tumor cells at a low virus to tumor cell ratio. Such NDV-modified tumor cells were found to have increased tumor immunogenicity and to be effective as tumor vaccines for antimetastatic therapy in combination with surgical removal of the primary tumor. Postoperative immunization with ESb-NDV led to the establishment of long-lasting systemic antitumor immunity (Schirrmacher and Heicappell 1987). Important parameters for optimal therapeutic effects were the time of operation of the primary tumor, the remaining residual disseminated tumor burden, and the dose of virus admixed with a standard dose of 107 irradiated tumor cells.
Keywords
- Newcastle Disease Virus
- Autologous Tumor
- Autologous Tumor Cell
- Active Specific Immunotherapy
- Optimal Therapeutic Effect
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ahlert T, Bastert G, Kaul S, Schirrmacher V (1988) Induktion einer antitumoralen Immunantwort beim Ovarialkarzinom mit virusmodifizierten autologen Tumorzellen. In: Verhandlungen der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe. 47. Kongreß München 6-10 September 1988
Bluming AZ, Ziegler JL (1971) Regression of Burkitt’s lymphoma in association with measles infection. Lancet 2:825
Bosslet K, Schirrmacher V, Shantz G (1979) Tumor métastases and cell-mediated immunity in a model system in DBA/2 mice. V Similar specificity patterns of protective anti-tumor immunity in vivo and of cytotoxic T cells in vitro. Int J Cancer 24:303–313
Brown GE, Simon EH, Chung C (1980) Interferon production by individual L cells. J Gen Virol 47:171–182
Cassel WA, Garret RE (1965) Newcastle Disease Virus as an anti-neoplastic agent. Cancer 18:863
Cassel WA, Murray DR, Torbin AH, Olkowsk ZL, Moore ME (1977) Viral oncolysate in the management of malignant melanoma. I. Preparation of the oncolysate and measurement of immunologic responses. Cancer 40:672–679
Cassel WA, Murray DR, Phillips H (1983) A phase II study on the postsurgical management of stage II malignant melanoma with a Newcastle Disease Virus Oncolysate. Cancer 52:856–860
Cassel WA, Weidenheim KM, Campbell WG, Murray DR (1986) Malignant Melanoma. Inflammatory mononuclear cell infiltrates in cerebral métastases during concurrent therapy with viral oncolysates. Cancer 57:1302–1312
Cassel WA, Murray DR (1988) Letter to the Editor. Nat Immun Cell Growth Regul (in press)
Collins PL, Hightower LE (1982) Newcastle Disease Virus stimulates the cellular accummu-lation of stress (heat shock) m-RNAs and proteins. J Virol 44:703–707
Cortesina G, De Stefani A, Giovarelli M, Garzia Barioglio M, Cavallo G, Jemma C, Forni G (1988) Treatment of recurrent cell carcinoma of head and neck with low doses of interleu-kin-2 (IL-2) injected perilymphatically. Cancer (in press)
DeMaeyer-Guignard J (1984) Effects of interferon on cell-mediated immunity as manifested by delayed hypersensitivity and allograft rejection. In: Vilcek J, DeMaeyer E (eds) Interferon, Interferons and the immune system, Vol 2, Elsevier, Amsterdam, pp 133–145
Evans R, Duffy T (1985) The immunological basis of tumor rejection: the absolute dependence of the effector arm on sensitized T cells after chemoimmunotherapy of a murine sarcoma. J Immunol 134:4255
Forni G, Santoni A, Giovarelli M (1984) Lymphokine activated tumor inhibition in vivo. I The local administration of interleukin-2 triggers non-reactive lymphocytes from tumor bearing mice to inhibit tumor growth. J Immunol 134:1305
Fowler JE (1986) Failure of immunotherapy for metastatic renal cell carcinoma. J Urol 135:22
Freedman RS, Bowen JM, Herson IM, Wharton JT, Edwards CL, Rutledge FN (1983) Immunotherapy for vulvar carcinoma with virus modified homologous extract. Obstet Gynecol 62:701–714
Gewert DR, Coulombe B, Castelino M, Skup D, Williams BRG (1987) Characterization and expression of a murine gene homologous to human EPA/TIMP: a virus-induced gene in the mouse. EMBO J 6:651–657
Hamburg SI, Cassell GH, Rabinovich M (1980) Relationship between enhanced macrophage phagocytic activity and the induction of interferon by Newcastle Disease Virus in mice. J Immunol 124:1360–1364
Hanna MG, Brandhorst JS, Peters LC (1979) Active specific immunotherapy of residual micrometastases. An evaluation of sources, doses and ratios of BCG with tumor cells. Cancer Immunol Immunother 7:165–173
Hanna MG, Peters LC, Brandhorst JS, Pollack VA (1980) Postoperative spezifische Immuntherapie von Rest-Mikrometastasen: Ergebnisse eines experimentellen Modells. Schwerpunkt Medizin (Suppl) 2
Hanna MG, Key ME (1982) Immunotherapy of metastases enhances subsequent chemotherapy. Science 217:367–369
Heicappell R, Schirrmacher V, von Hoegen P, Ahlert T, Appelhans B (1986) Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I. Parameters for optimal therapeutic effects. Int J Cancer 37:569–577
Hersey P, Edwards A, D’Alessandro G, MacDonald M (1986) Phase II study of vaccina melanoma cell lysates (VMCL) as adjuvant to surgical treatment of stage II melanoma. II. Effects on cell mediated cytotoxicity and leucocyte dependent antibody activity: immunological effects of VMCL in melanoma patients. Cancer Immunol Immunother 22:221–231
Hersey P, Edward A, Coates A, Shaw H, McCarthy W, Milton G (1987) Evidence that treatment with vaccinia-melanoma cell lysates (VMCL) may improve survival of patients with stage II melanoma. Cancer Immunol Immunother 25:257–265
Hirsch R, Zakay-Rones Z, Huszar M, Shoham J (1988) Induction of strong antitumor immunity by non-lytic viral infection of murine tumor cells. Cancer Res (in press)
Hollinshead A, Stewart THM, Takita H, Dalbow M, Concannon J (1987) Adjuvant specific active lung cancer immunotherapy trials. Tumor-associated antigens. Cancer 60:1249–1262
Hoover HC Jr, Sudyke M, Dangel R, Peters LC, Hanna MG Jr (1984) Delayed cutaneous hypersensitivity to autologous tumor cells in colorectal cancer patients immunized with an autologous tumor cell: bacillus Calmette-Guérin vaccine. Cancer Res 44:1671–1676
Hoover HC Jr, Surdyke MG, Dangel RB, Peters LC, Hanna MG (1985) Prospectively randomized trial of adjuvant active specific immunotherapy for human colorectal cancer. Cancer 55:1263–1243
Klippel KF, Jacobi GH, Schulte-Wissermann H (1981) Aktive Immunotherapie beim meta-stasierenden Hypernephrom. Akt Urol 12:161
Kobayashi H (1979) Viral xenogenization of intact tumor cells. Adv Cancer Res 30:279–299
Kurth KH, Marguet R, Zwartendijk J, Warnaar SO (1987) Autologous anticancer antigen preparation for specific immunotherapy in advanced renal cell carcinoma. Eur Urol 13:103–109
Lehner B, Liebrich W, Möller P, Schirrmacher V, Schlag P (1988) Active specific immunotherapy in colorectal cancer with autologous tumor cells and NDV - which dose is the best? Clin Exp Metastasis (Suppl 1) 6:83–84
Liebrich W, Lehner B, Möller P, Schirrmacher V, Schlag P (1988) Preparation and characterization of a new type of tumor cell vaccine: surface modified human colon cells using Newcastle Disease Virus (NDV). Clin Exp Metastasis (Suppl 1) 6:80–81
Lindenmann J (1984) Viruses as immunological adjuvants in cancer. Biochem Biophys Act 355:49–75
Lorence RM, Rood PA, Kelly KW (1988) Newcastle Disease Virus as an antineoplastic agent. Induction of Tumor-Necrosis-Factor a and augmentation of TNF a cytotoxicity. J Natl Cancer Inst 114 (Suppl):40
Lotzova E, Savary CA, Freedman RS, Bowen JM (1984) Natural Killer cell cytotoxic potential of patients with ovarian carcinoma and its modulation with virus-modified tumor cell extracts. Cancer Immunol Immunother 17:124–129
Marcus PI, Svitlik C, Selellick MJ (1983) Interferon induction by viruses. X. A model for interferon induction by Newcastle Disease Virus. J Gen Virol 64:2419–2431
Mathé G, DeVassal F, Delgado M, Pouillard P, Belpomme D, Joseph R, Schwarzenberg L, Amiel JL, Schneider M, Cattan A, Musset M, Misset JL, Yasmin C (1976) Current results of the first 100 cytologically typed acute lymphoid leukemia submitted to BCG active immunotherapy. Cancer Immunol Immunother 1:77
McCune CS, Patherson WB, Henshaw EC (1979) Active specific immunotherapy with tumor cells and corynebacterium: a phase I study. Cancer 43:1916
McCune CS, DeKernion JB, Hüben RP, Poutes JE (1984) Specific immunotherapy vs. Megace for metastatic renal cell carcinoma. A prospective randomized trial. J Urol 131:178A
Merigan TC, DeClercq E, Finkelstein MS, Clever L, Walker S, Waddell DJ (1970) Clinical studies employing interferon inducers in man and animals. Am NY Acad Sci 173:746–759
Moore AE (1955) Effects of viruses on tumors. Am Rev Microbiol 393–410
Murray DR, Cassel WA, Torbin A, Olkowski Z, Moore ME (1977) Viral oncolysate in the management of malignant melanoma. II. Clinical studies. Cancer 40:680–686
Rees RC, Dalton BJ, Young JF, Hanna N, Poste G (1987) Augmentation of human natural killer cell activity by influenza virus antigens produced in Escherichia coli. J Biol Response Mod 6:69–87
Rolle, Mayr (1984) In: Mayr A (ed) Medizinische Mikrobiologie, Infektions- und Seuchenlehre für Tierärzte, Biologen und Agrarwissenschaftler. Stuttgart.
Salmon P, Baix (1922) Vaccine varioloque dans le cancer. C R Soc Biol (Paris) 86:819–820
Schärfe T, Becht E, Klippel KF, Jacobi GH, Hohenfeller R (1986) Active immunotherapy of stage IV renal cell cancer using autologous tumor cells. World J Urol 3:245–248
Schild HJ, von Hoegen P, Schirrmacher V (1989) Modification of tumor cells by a low dose of Newcastle Disease Virus. II. Augmented tumor specific T cell response as a result of CD4+ and CD8+ immune T cell cooperation. Cancer Immunol Immunother 28:22–28
Schirrmacher V, Shantz G, Clauer K, Komitowski D, Zimmermann HP, Lohmann-Matthes ML (1979) Tumor métastases and cell-mediated immunity in a model system in DBA/2 mice. I. Tumor invasiveness in vitro and metastases formation in vivo. Int J Cancer 23:233–244
Schirrmacher V, Fogel M, Russmann E, Bosslet K, Altevogt P, Beck L (1982) Antigenic variation in cancer metastasis. Immune escape versus immune control. Cancer Metastasis Rev 1:241–274
Schirrmacher V, Ahlert T, Heicappell R, Appelhans B, von Hoegen P (1986) Successful application of non-oncogenic viruses for antimetastatic cancer immunotherapy. Cancer Rev 5:19–49
Schirrmacher V (1986) Postoperative activation of tumor specific T cells as a means to achieve immune control of minimal residual disease. In: Fortner JG, Rhoads JE (eds) Accomplishments in cancer research 1986. General Motors Cancer Research Foundation, pp 218–232. Lippincott, Philadelphia
Schirrmacher V, Heicappell R (1987) Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. II. Establishment of specific systemic anti tumor immunity. Clin Exp Metastasis 5: (2) 147–156
Sinkovics JG (1977) Immunotherapy with viral oncolysates for sarcoma. JAMA 237:869
Skornick YG, Rong GH, Sindelar WF, Richert L, Klausner JM, Rozin RR, Shinitzky M (1984) Active immunotherapy of human solid tumor with autologous cells treated with cholesteryl hemisuccinate. A phase I study. Cancer 58:650–654
Southam CM (1960) Present status of oncolytic virus studies. Trans NY Acad Sci Ser 2 22:687–693
Tallberg T (1974) Cancer immunotherapy by means of polymerized autologous tumor tissue with special references to some patients with pulmonary tumour. Scand J Resp Dis (Suppl) 89:107–122
Tallberg T, Kalina T, Halttunen P, Tykkä H, Mahlberg K, Matous B, Sundeil B (1986) Postoperative specific immunotherapy with supportive measures in patients suffering from recurrent metastasized melanoma. J Surg Oncol 33:115–119
Tallberg T, Tykkä H (1986) Specific active immunotherapy in advanced renal cell carcinoma. A clinical longterm follow-up study. World J Urol 3:234–244
Tallberg T, Kalina T, Halttunen P, Mahlberg K, Tykkä H, Seiro J, Dabek J (1987) Postoperative active specific immunotherapy with supportive biomodulating measures in patients suffering from malignant gastric tumors. Tumor Diagnost Ther 8:49–53
Tykkä H, Hjelt L, Oravisto KJ, Turunen M, Tallberg T (1974) Disappearance of lung métastases during immunotherapy in 5 patients suffering from renal carcinoma. Scand J Resp Dis (Suppl) 89:123
von Hoegen P, Weber E, Schirrmacher V (1988b) Modification of tumor cells by a low dose of Newcastle Disease Virus: I Augmentation of the tumor-specific T cell response in the absence of an anti-viral response. Eur J Immunol 18:1159–1166
von Hoegen P, Heicappell R, Griesbach A, Altevogt P, Schirrmacher V (1988a) Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. III. Postoperative activation of tumor specific CTLP from mice with metastases requires stimulation with the specific antigen plus additional signals. Invasion Metastasis 9, 117–133
Wallack MK, McNally KR, Lefthereriotis E, Seigler H, Balch CH, Wanebo H, Bartolucci AA, Bash JA (1986) A southeastern cancer study group phase I/II trial with vaccinia melanoma oncolysates. Cancer 57:649–655
Waterson AP, Pennington TH, Allan BH (1967) Virulence in Newcastle Disease Virus. Br Med Bull 23:123
Westly HJ, Kleiss AJ, Kelley KW, Wong PKY, Yuen PH (1986) Newcastle Disease Virus-infected splenocytes express the proopiomelanocortin gene. J Exp Med 163:1589–1594
Wunderlich M, Schiessel R, Rainer H, Rauhs R, Kovats E, Schemper M, Dittrich Ch, Micksche M, Sedlacek HH (1985) Effect of adjuvant chemo- or immunotherapy on the prognosis of colorectal cancer operated for cure. Br J Surg (Suppl) 72:107–110
Zangemeister U, Thiede K and Schirrmacher V (1989) Recruitment and activation of tumor-specific immune T cells in situ: Functional studies using a sponge matrix model. Int. J. Cancer 43, 310–316
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Schirrmacher, V. et al. (1989). Active Specific Immunotherapy with Autologous Tumor Cell Vaccines Modified by Newcastle Disease Virus: Experimental and Clinical Studies. In: Schirrmacher, V., Schwartz-Albiez, R. (eds) Cancer Metastasis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74236-1_20
Download citation
DOI: https://doi.org/10.1007/978-3-642-74236-1_20
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-50471-9
Online ISBN: 978-3-642-74236-1
eBook Packages: Springer Book Archive