RECOMBINANT BCG THERAPY SUPPRESSES MELANOMA TUMOR-GROWTH

被引:24
作者
DUDA, RB [1 ]
YANG, H [1 ]
DOOLEY, DD [1 ]
ABUJAWDEH, G [1 ]
机构
[1] HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02215
关键词
MELANOMA; VACCINE; BCG; IMMUNOTHERAPY; GENE TRANSFER; CYTOKINES;
D O I
10.1007/BF02307089
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Melanoma is the fastest rising cancer in the United States. Bacillus Calmette-Guerin (BCG) has been genetically engineered to actively express and secrete the cytokine interleukin-2 (IL-2). Both BCG and IL-2 have known potent antitumor and immunomodulatory properties. Methods: This recombinant BCG (rBCG 3A) has been tested as an intratumoral injection and a vaccine therapy in conjunction with irradiated tumor cells against melanoma in the murine B16 melanoma moder. Results: The transfection process did not adversely alter the function of the wild-type (WT) BCG. rBCG 3A and WT BCG are equally effective intratumoral and vaccine therapies against melanoma when compared with normal saline control groups. Tumor burdens were significantly smaller (p less than or equal to 0.01 and 0.05) for the treatment groups for both intratumoral and vaccine administration of therapy. Immunization with rBCG 3A and WT BCG 14 days before a B16 challenge resulted in an similar to 45% smaller tumor burden when compared with controls. Conclusions: Novel therapies based on the immunogenic properties of melanoma combined with molecular technologies may offer promise for an effective and safe treatment of melanoma.
引用
收藏
页码:542 / 549
页数:8
相关论文
共 54 条
  • [1] CYTOKINES - FROM CLONE TO CLINIC
    AGGARWAL, BB
    POCSIK, E
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1992, 292 (02) : 335 - 359
  • [2] HUMORAL AND CELL-MEDIATED IMMUNE-RESPONSES TO LIVE RECOMBINANT BCG-HIV VACCINES
    ALDOVINI, A
    YOUNG, RA
    [J]. NATURE, 1991, 351 (6326) : 479 - 482
  • [3] EXPRESSION OF MURINE INTERLEUKIN-7 IN A MURINE GLIOMA CELL-LINE RESULTS IN REDUCED TUMORIGENICITY INVIVO
    AOKI, T
    TASHIRO, K
    MIYATAKE, S
    KINASHI, T
    NAKANO, T
    ODA, Y
    KIKUCHI, H
    HONJO, T
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (09) : 3850 - 3854
  • [4] ASHER AL, 1991, J IMMUNOL, V146, P3227
  • [5] NONSPECIFIC AND SPECIFIC ACTIVE IMMUNOTHERAPY IN A B-16 MURINE MELANOMA SYSTEM
    AVENT, J
    VERVAERT, C
    SEIGLER, HF
    [J]. JOURNAL OF SURGICAL ONCOLOGY, 1979, 12 (01) : 87 - 96
  • [6] TREATMENT OF METASTATIC MELANOMA WITH AN AUTOLOGOUS TUMOR-CELL VACCINE - CLINICAL AND IMMUNOLOGICAL RESULTS IN 64 PATIENTS
    BERD, D
    MAGUIRE, HC
    MCCUE, P
    MASTRANGELO, MJ
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1990, 8 (11) : 1858 - 1867
  • [7] DISSECTING THE IMMUNOBIOLOGICAL EFFECTS OF BACILLUS-CALMETTE-GUERIN (BCG) IN-VITRO - EVIDENCE OF A DISTINCT BCG-ACTIVATED KILLER (BAK) CELL PHENOMENON
    BOHLE, A
    THANHAUSER, A
    ULMER, AJ
    ERNST, M
    FLAD, HD
    JOCHAM, D
    [J]. JOURNAL OF UROLOGY, 1993, 150 (06) : 1932 - 1937
  • [8] ELEVATIONS OF CYTOKINES INTERLEUKIN-1, INTERLEUKIN-2 AND TUMOR-NECROSIS-FACTOR IN THE URINE OF PATIENTS AFTER INTRAVESICAL BACILLUS CALMETTE-GUERIN IMMUNOTHERAPY
    BOHLE, A
    NOWC, C
    ULMER, AJ
    MUSEHOLD, J
    GERDES, J
    HOFSTETTER, AG
    FLAD, HD
    [J]. JOURNAL OF UROLOGY, 1990, 144 (01) : 59 - 64
  • [9] ADJUVANT IMMUNOTHERAPY WITH BCG IN STAGE-II MALIGNANT-MELANOMA
    BYRNE, MJ
    VANHAZEL, G
    REYNOLDS, PM
    LEMISH, WM
    HOLMAN, CDJ
    [J]. JOURNAL OF SURGICAL ONCOLOGY, 1983, 23 (02) : 114 - 116
  • [10] BYSTRYN JC, 1978, J IMMUNOL, V120, P96