Advertisement

Cancer Immunology, Immunotherapy

, Volume 35, Issue 5, pp 325–330 | Cite as

Active specific immunotherapy with Newcastle-diseasevirus-modified autologous tumor cells following resection of liver metastases in colorectal cancer

First evaluation of clinical response of a phase II-trial
  • Peter Schlag
  • Maria Manasterski
  • Thomas Gerneth
  • Peter Hohenberger
  • Margret Dueck
  • Christian Herfarth
  • Winfrid Liebrich
  • Volker Schirrmacher
Original articles

Summary

A group of 23 colorectal cancer patients were treated by a new type of active specific immunotherapy (ASI) following complete surgical resection of liver metastases (R0 resection). For ASI treatment we used a vaccine consisting of 1 × 107 autologous, irradiated (200 Gy) metastases-derived tumor cells incubated with 32 hemagglutination units (HU) of Newcastle disease virus (NDV). The adjuvant vaccine therapy was started 2 weeks after surgery and was repeated five times at 14-days intervals followed by one boost 3 months later. The delayed-type hypersensitivity (DTH) skin reactions to the vaccine were measured as well as the DTH reactions to a challenge test of 1 × 107 non-virus-modified autologous tumor cells from liver metastases or 1 × 107 autologous normal liver cells. In addition 32 HU NDV alone and a standard antigen test (Merieux test) were applied pre- and post-vaccination. The vaccination was well tolerated. In 13 of 23 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. Nine patients (40%) experienced an increased DTH reactivity against autologous tumor cells following vaccination, while 17% or fewer showed an increased reactivity to Merieux test antigens, NDV, or normal liver cells. The increased antitumor response was not correlated to responsiveness to NDV alone, autologous liver cells, enzymes and culture medium used for vaccine preparation or standard antigens (Merieux test). After a follow-up of at least 18 months 61% of the vaccinated patients developed tumor recurrence in comparison to 87% of a matched control groups from the same institution that had been only surgically treated. The results of this phase II trial are encouraging and should stimulate further prospective randomized studies.

Key words

Active specific immunotherapy Colorectal cancer Liver metastases 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Berd D, Maguire HC Jr, McCue P, Mastangelo MJ (1990) Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. J Clin Oncol 8: 1858Google Scholar
  2. 2.
    Bohle W, Schlag P, Liebrich W, Hohenberger P, Manasterski M, Möller P, Schirrmacher V (1990) Postoperative active specific immunization in colorectal cancer patients with virus-modified autologous tumor-cell vaccines. First clinical results with tumor-cell vaccines modified with life but avirulent Newcastle disease virus. Cancer 66: 1517Google Scholar
  3. 3.
    Cassel WA, Murray PR, Philipps HS (1983) A phase II study on the postsurgical management of stage II malignant melanoma with Newcastle disease virus oncolysate. Cancer 52: 856Google Scholar
  4. 4.
    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. Int J Cancer 37: 569Google Scholar
  5. 5.
    Hodgson WJB, Mittelman A, Katz S (1986) Treatment of colorectal hepatic metastases by intrahepatic chemotherapy alone or as an adjuvant to complete or partial removal of metastatic disease. Ann Surg 203: 420Google Scholar
  6. 6.
    Hoover HC, Surdyke MG, Dangel RB, 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: 1671Google Scholar
  7. 7.
    Hoover HC, Surdyke MG, Dangel RB, Peters LC, Hanna MG Jr (1985) Prospectively randomized trial of adjuvant active-specific immunotherapy for human colorectal cancer. Cancer 55: 1236Google Scholar
  8. 8.
    Hughes KS, Simon R, Songhorabodi S (1986) Resection of the liver for colorectal carcinoma metastases: a multiinstitutional study of patterns of recurrences. Surgery 100: 278Google Scholar
  9. 9.
    Hughes KS, Rosenstein RB, Songhorabodi S (1988) Resection of the liver for colorectal carcinoma metastases: a multiinstitutional study of long-term survivors. Dis Colon Rectum 31: 1Google Scholar
  10. 10.
    Jessup JM, McBride CM, Ames FC Guarda L, Ota DM, Romsdahl MM. Martin MM Jr (1986) Active specific immunotherapy of Dukes B and C colorectal carcinoma: comparison of two doses of the vaccine. Cancer Immunol Immunother 21: 233Google Scholar
  11. 11.
    Kemeny MM, Goldberg D, Beatty JD, Blayney D, Browning S, Doroschow J, Ganteaume L, Hill RC, Kokal WA, Riihmaki DU, Terz JJ (1986) Results of a prospective randomized trial of continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries. Cancer 57: 492Google Scholar
  12. 12.
    Kniker WT, Anderson CT, Roumiantzeff M (1979) The multi-test system: a standardized approach to evaluation of delayed hypersensitivity and cell-mediated immunity. Ann Allergy 43: 73Google Scholar
  13. 13.
    Lehner B, Schlag P, Liebrich W, Schirrmacher V (1990) Postoperative active specific immunization in curatively resected colorectal cancer patients with a virus-modified autologous tumor cell vaccine. Cancer Immunol Immunother 32: 173Google Scholar
  14. 14.
    Lesourd B, Winters WD (1982) Specific immune response to skin test antigens following repeated multiple antigen skin tests in normal individuals. Clin Exp Immunol 50: 635Google Scholar
  15. 15.
    Liebrich W, Schlag P, Manasterski M, Lehner B, Stöhr M, Möller P, Schirrmacher V (1991) In vitro and clinical characterization of a Newcastle disease virus-modified autologous tumor cell vaccine for treatment of colorectal cancer patients. Eur J Cancer 27: 703Google Scholar
  16. 16.
    Lotzowa 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 extract. Cancer Immunol Immunother 17: 124Google Scholar
  17. 17.
    McCune CC, O'Donnell RW, Marquis DM, Sahasrabudhe DM (1990) Renal cell carcinoma treated by vaccines for active specific immunotherapy: a correlation of survival with skin testing by autologous tumor cells. Cancer Immunol Immunother 32: 62Google Scholar
  18. 18.
    Schild HJ, von Hoegen P, Schirrmacher V (1988) 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: 22Google Scholar
  19. 19.
    Schirrmacher V (1986) Postoperative activation of tumor specific T cells as a means to achieve immune control of minimal residual disease. In: JG Fortner, Rhoads IE (eds) General Motors Cancer Research Foundation, p 218Google Scholar
  20. 20.
    Schlag P, Hohenberger P, Herfarth Ch (1990) Resection of liver metastases in colorectal cancer — comparative analysis of treatment results in synchronous versus metachronous metastases. Eur J Surg Oncol 16: 360Google Scholar
  21. 21.
    Stoeck M, Marland-Noske C, Manasterski M, Zwatzke H, Horn S, Möbius V, Schlag P, Schirrmacher V (1992) Phenotypic and functional analysis of T lymphocyte microcultures obtained from the vaccination sites of cancer patients undergoing active specific immunization (ASI) with autologous NDV-modified tumor cells. (in press)Google Scholar
  22. 22.
    von Hoegen P, Zawatzky R, Schirrmacher V (1990) Modification of tumor cells by a low dose of Newcastle disease virus: III. Potentiation of tumor specific cytolytic T cell reactivity via induction of interferon α, β. Cell Immunol 126: 80–90Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Peter Schlag
    • 1
  • Maria Manasterski
    • 1
  • Thomas Gerneth
    • 1
  • Peter Hohenberger
    • 2
  • Margret Dueck
    • 1
  • Christian Herfarth
    • 2
  • Winfrid Liebrich
    • 1
  • Volker Schirrmacher
    • 3
  1. 1.Section of Surgical OncologyUniversity of HeidelbergHeidelbergGermany
  2. 2.Department of SurgeryUniversity of HeidelbergHeidelbergGermany
  3. 3.German Cancer Research CenterDivision of Genetics and ImmunologyHeidelbergGermany

Personalised recommendations