A southeastern cancer study group phase I/II trial with vaccinia melanoma oncolysates

Wallack, Marc K.; McNally, Katherine R.; Leftheriotis, E; Seigler, Hilliard F.; Balch, Charles M.; Wanebo, Harold J.; Bartolucci, Alfred A.; Bash, Jerry A.

doi:10.1002/1097-0142(19860201)57:3<649::aid-cncr2820570342>3.0.co;2-6

Cited by 67 publications

(15 citation statements)

References 4 publications

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“…Attempts have been made to elicit tumor immunity through inoculation of purified antigens or tumor lysates (1)(2)(3)(4)(5)(6)(7) or anti-idiotypic antibodies directed against tumor-associated antigens (8)(9)(10). Such approaches have met with only limited success, and we have used instead live recombinant vaccinia viruses expressing tumor antigens to immunize against tumor cells.…”

mentioning

confidence: 99%

Vaccination against tumor cells expressing breast cancer epithelial tumor antigen.

Hareuveni

Gautier

Kiény

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Ninety-one percent of breast tumors aberrantly express an epithelial tumor antigen (ETA) identified by monoclonal antibody H23. Vaccinia virus recombinants expressing tumor antigens have considerable promise in the active immunotherapy of cancer, and we have evaluated the potential of vaccinia recombinants expressing the secreted (S) and cell-associated (transmembrane, T) forms of H23 ETA to elicit immunity to tumor cells expressing ETA. Tumorigenic ras-transformed Fischer rat fibroblast lines FR-S and FR-T, expressing the S or T form of H23 ETA, respectively, were constructed for use in challenge experiments. Expression of H23 ETA in these lines was confirmed by Western blotting and immunofluorescence. When challenged by subcutaneous seeding of tumor cells, 97% (FR-S) and 91% (FR-T) of syngeneic Fischer rats rapidly developed tumors that failed to regress. Vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S. The vaccinia recombinant expressing the S form was a less effective immunogen, and vaccination protected only 29-30% of animals from developing tumors upon challenge with either FR-S or -T cells. The increased immunogenicity of the recombinant expressing ETA-T was reflected in elevated levels of ETA-reactive antibody in vaccinated animals, confirming that secreted antigens expressed from vaccinia virus are less effective immunogens than their membrane-associated counterparts.

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mentioning

confidence: 99%

Vaccination against tumor cells expressing breast cancer epithelial tumor antigen.

Hareuveni

Gautier

Kiény

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…162,163 The later 1970s saw the evolution of other forms of melanoma vaccination, including the use of oncolysates prepared from surgically excised autologous melanoma infected with the Newcastle disease virus or vaccinia virus. 164,165 By that time, it had been reported that this and other viruses could induce the production of interferon, 166 so the stage was set for the advent of interferon in melanoma therapy. In Cancer in 1983, Retsas et al reported a single response among 17 pretreated melanoma patients receiving human lymphoblastoid interferon, 167 and the next year Creagan et al reported a 31-patient trial of highdose recombinant interferon-a, given intramuscularly 3 times weekly, with 7 objective responses but substantial toxicity, predominantly constitutional.…”

Section: Immunologic Therapies In Melanomamentioning

confidence: 89%

State of the science 60th anniversary review

Demierre

Sabel

Margolin

et al. 2008

Cancer

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“…Procedural details for cell isolation, growth and infection with vaccinia, preparation of the oncolysate have been described elsewhere [19][20][21]. The rationale of such a scheme was entrenched in basic viral processes of budding whereby the virus always 'pinches' membrane proteins.…”

Section: Multivalent Cancer Vaccine Using Vaccinia Based Antigen Retrmentioning

confidence: 99%

Cancer Vaccines: Bench to Bedside

Tuli

Maniyar

Bednarczyk

et al. 2016

IJTS

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The immune system has immense potential in cancer therapy as it is individualized, precision driven and robust, however, it is associated with challenges of its own that include immune evasion, development of tolerance and a sustained tumor rejection response. Recent FDA approval of several checkpoint inhibitors, anti-CTLA4, anti-PD-1, has re-invigorated cancer immunology by demonstrating that tolerance to cancer can be broken to induce a sustained immune response in patients. Active immunization with multivalent tumor associated antigens (TAA), however, is still a challenge. We have developed two specific distinct methods to generate multivalent antigens capable of tumor regression in prostate cancer and melanoma. In prostate cancer, we have generated specific multivalent peptide mimetics using phage display synthetic peptide libraries capable of metastatic tumor regression in an animal model. In melanoma, we have used a vaccinia virus based antigen retrieval technology to generate a multivalent antigenic vaccine. The antigenic repertoire is well defined. A protocol for the melanoma vaccine is FDA approved for clinical Science, Vol. 2016, 33-60. doi: 10.13052/ijts2246-8765.2016.003 c 2016 34 N. Tuli et al. trials. We envision defining the humoral and cellular immune response to combine our active vaccine strategy with other treatment modalities including approved checkpoint inhibitors anti-CTLA4 and anti-PD-1. We believe our vaccine candidates are a new generation of immune-therapeutics that can prolong cancer free survival and prevent secondary recurrences. Our studies have challenged the existing paradigms to re-define cancer immunotherapy that bridges the gap between humoral and cellular immunity by combining active immune response with negative checkpoint inhibitors thus activating pre-existing dormant immune response. International Journal of Translational

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A southeastern cancer study group phase I/II trial with vaccinia melanoma oncolysates

Cited by 67 publications

References 4 publications

Vaccination against tumor cells expressing breast cancer epithelial tumor antigen.

Vaccination against tumor cells expressing breast cancer epithelial tumor antigen.

State of the science 60th anniversary review

Cancer Vaccines: Bench to Bedside

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