Preimmunization of mice with formalinized extracellular antigens of melanoma in combination with IL‐2 and surgical resection increased survival and tumor control in metastatic melanoma model

Shrayer, David; Koness, James; Kouttab, Nichola; Bogaars, Hendrik A.; Hearing, Vincent J.; Gersten, Douglas M.; Maizel, Abby; Wanebo, Harold J.

doi:10.1002/jso.2930520303

Cited by 7 publications

(4 citation statements)

References 17 publications

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“…Mean survival time (days) in both of these groups was higher than in control and in the other experimental groups, but survival rate was a little higher in Group 5 (50% of mice survived at the 13th week) than in Group 4 (40% of mice survived at the 12th week). Effective antitumor combinations of IL‐12 with different nonspecific adjuvant‐vaccines (12–15) showed the future possibility to combine mIL‐12 with experimental specific antimelanoma vaccines similar to what was described earlier when vaccines were combined with IL‐2 (16–18). The possibility of combining melanoma vaccines with IL‐12 has special interest because of successful augmentation of NK cells against human melanoma in immunodeficient mice by combination of IL‐12 with IL‐2 (7).…”

Section: Discussionmentioning

confidence: 87%

Capacity of murine IL‐12 to inhibit the development of primary melanoma tumors and to prevent lung metastases in the melanoma‐challenged mice

et al. 2002

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Interleukin-12 (IL-12) has the capacity to activate cytotoxic lymphocytes, stimulate natural killer cells, induce the production of INF-gamma, and be synergistic with IL-2. We have evaluated this cytokine in an experimental model for metastatic melanoma that approximates the major clinical stages of metastatic dissemination. To develop primary melanoma tumors, mice were injected subcutaneously with 5 x 10(5) cells in a volume of 25 microliters into the middle of the tail (11). In a month, mice were started to be treated for 4 weeks with recombinant murine IL-12 (R mIL-12) at the following doses: 0, 0.5, 2.5, 5.0, 15.0, and 50 micrograms/kg. Diameters of the primary melanoma tumors were measured at weekly intervals. At the end of 13 weeks (9 weeks from the start of treatment with R mIL-12), all surviving mice were sacrificed. Pathological examination of lung metastases (macroscopy) was done with all dead or sacrificed mice. Treatment of mice bearing melanoma at a dose of 300 ng/mouse (15 micrograms/kg) inhibited development of primary tumors in 40% of mice. The primary tumor diameters were significantly lower in the group treated with 300 ng/mouse (15 micrograms/kg) in comparison to controls. At the end of the observation period, groups treated with 0.5, 2.5, 15.0, and 50 micrograms/kg had mean primary tumor diameters smaller than the control group. Evaluation of IL-12 therapy on primary tumor growth, mean diameters of primary tumors, survival rate, and development of lung metastases showed that the best results were observed using 300 ng/mouse (15 micrograms/kg) R mIL-12.

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Section: Discussionmentioning

confidence: 87%

Capacity of murine IL‐12 to inhibit the development of primary melanoma tumors and to prevent lung metastases in the melanoma‐challenged mice

et al. 2002

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“…Vaccines tested included ECA (extracellular antigen) proteins shed by melanoma cells into serumfree culture supernatants over a 3 day period; comparable protein fractions shed by fibrosarcoma cells are used as a control (14)(15)(16). Intact cells (either melanoma or fibrosarcoma) are also used in immunization protocols.…”

Section: Vaccine Preparationmentioning

confidence: 99%

“…In such studies, the mice were immunized with the various vaccines over a four week period prior to challenge with the melanoma. Following that time, the tails and thus the primary tumors were removed surgically and survival of the mice was then measured (15). Control mice developed large tumors on the resected tails and many metastases were visible.…”

Section: Vaccine Therapymentioning

confidence: 99%

“…In complementary experiments, we have characterized monovalent (i.e. B700) and polyvalent melanoma antigen vaccines that have also shown promise in therapeutic regimens (14)(15)(16). The usefulness of our antimelanoma vaccine has been shown to be potentiated by treatment with formalin, a treatment that has often been used with viral and bacterial preparations to enhance their immunogenic effects.…”

Section: Introductionmentioning

confidence: 99%

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Novel Experimental Approaches to Melanoma Diagnosis and Therapy

Hearing

Gersten

Shrayer

et al. 1994

The Journal of Dermatology

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We have investigated the potential use of immune therapies on the growth of melanoma metastases in a new animal model that more closely approximates the clinical situation. We have found that significant benefits towards decreased metastatic growth and subsequent animal survival can be achieved by treatment of tumor-bearing mice with melanoma-specific monoclonal antibodies or alternatively, with various types of monovalent or polyvalent vaccines. The beneficial effects of those vaccines can be significantly enhanced by concomitant interleukin-2 therapy.

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Nude mouse model to study passive humoral immunotherapy directed against B16 F10 murine melanoma

Shrayer

Bogaars

Gersten

et al. 1994

Journal of Surgical Oncology

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A model to study passive humoral immunotherapy of experimental melanoma was generated by subcutaneous injection of B16 F10 murine melanoma cells in the midtail of BALB/C nude (nu/nu) mice. Mice were challenged with melanoma cells pretreated: (1) with complete culture medium, (2) with 10% adjuvant control serum, (3) with 10% anti-fECA (formalinized extracellular antigens) immune serum, or (4) with a monoclonal antibody (mAB H2-3-3) specific for the B700 melanoma-associated antigen. All control mice challenged with melanoma cells pretreated either with culture medium or with medium containing adjuvant control serum (Groups I and II) died during the observation period of 84 days. At day 84, 60% of the mice challenged with melanoma cells pretreated with anti-fECA immune serum (Group III) survived, as did 100% of the mice challenged with cells pretreated with mAb H2-3-3 (Group IV). Injection of melanoma cells pretreated with mAb H2-3-3 was associated with the greatest reduction of subsequent local tumor growth and the lowest number of metastatic lung tumors. The inhibitory effects of immune sera in vivo also correlated with in vitro effects of anti-fECA immune serum and mAb H2-3-3, determined on B16 F10 melanoma target cells using assays for DNA synthesis and antibody dependent cellular cytotoxicity (ADCC). In sum, this nude mouse model for the study of passive humoral immunotherapy of experimental melanoma was utilized to demonstrate significant protective effects against B16 F10 melanoma cell challenge by treatment with anti-fECA immune sera or a melanoma-specific monoclonal antibody.

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Preimmunization of mice with formalinized extracellular antigens of melanoma in combination with IL‐2 and surgical resection increased survival and tumor control in metastatic melanoma model

Cited by 7 publications

References 17 publications

Capacity of murine IL‐12 to inhibit the development of primary melanoma tumors and to prevent lung metastases in the melanoma‐challenged mice

Capacity of murine IL‐12 to inhibit the development of primary melanoma tumors and to prevent lung metastases in the melanoma‐challenged mice

Novel Experimental Approaches to Melanoma Diagnosis and Therapy

Nude mouse model to study passive humoral immunotherapy directed against B16 F10 murine melanoma

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