BCG lmmunotherapy of Malignant Melanoma

Morton, Donald L.; Eilber, Frederick R.; Holmes, E. Carmack; Hunt, John S.; Ketcham, Alfred S.; Silverstein, Melvin J.; Sparks, Frank C.

doi:10.1097/00000658-197410000-00029

Cited by 400 publications

(87 citation statements)

References 10 publications

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“…Certain neoplasms, such as melanoma or renal cell carcinoma, are relatively more immunogenic, presumably through recognition of mutant gene products that arise in these cells. Conventional approaches to immunotherapy have used cytokines, adjuvants, or adoptive immune cell therapy in animal models (21)(22)(23)(24) and in humans (25)(26)(27). More recently, the potential of molecular genetic interventions to improve the efficacy of immunotherapy has been explored (15,28,29).…”

Section: Discussionmentioning

confidence: 99%

Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA–liposome complexes

Nabel

Gordon

Bishop

et al. 1996

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

222

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Analysis of the antitumor immune response after gene transfer of a foreign major histocompatibility complex class I protein, HLA-B7, was performed. Ten HLA-B7-negative patients with stage IV melanoma were treated in an effort to stimulate local tumor immunity. Plasmid DNA was detected within treated tumor nodules, and RNA encoding recombinant HLA-B7 or HLA-B7 protein was demonstrated in 9 of 10 patients. T cell migration into treated lesions was observed and tumorinfiltrating lymphocyte reactivity was enhanced in six of seven and two of two patients analyzed, respectively. In contrast, the frequency of cytotoxic T lymphocyte against autologous tumor in circulating peripheral blood lymphocytes was not altered significantly, suggesting that peripheral blood lymphocyte reactivity is not indicative of local tumor responsiveness. Local inhibition of tumor growth was detected after gene transfer in two patients, one of whom showed a partial remission. This patient subsequently received treatment with tumor-infiltrating lymphocytes derived from gene-modified tumor, with a complete regression of residual disease. Thus, gene transfer with DNA-liposome complexes encoding an allogeneic major histocompatibility complex protein stimulated local antitumor immune responses that facilitated the generation of effector cells for immunotherapy of cancer.

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Section: Discussionmentioning

confidence: 99%

Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA–liposome complexes

Nabel

Gordon

Bishop

et al. 1996

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

222

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“…Historically, this has been observed in clinical trials of intralesional Bacilus Calmette Guerin (BCG) and various cytokine-based intralesional therapies. A longitudinal experience from the 1970s reported regression of 90% of lesions injected with BCG and 17% of noninjected lesions [15]. A study of adjuvant BCG for high-risk, resected disease did not show improved clinical outcomes, so this therapy is not used clinically as an adjuvant therapy [16].…”

Section: Rationale For Injectable Immune Therapymentioning

confidence: 99%

Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Melanoma

2015

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Melanoma often spreads to cutaneous or subcutaneous sites that are amenable to direct, intralesional injection. As such, developing effective injectable agents has been of considerable interest. Talimogene laherperepvec (T-VEC) is an injectable modified oncolytic herpes virus being developed for the treatment of advanced melanoma. Pre-clinical studies have shown that T-VEC preferentially infects melanoma cells and exerts antitumor activity through directly mediating cell death and by augmenting local and even distant immune responses. T-VEC has now been assessed in Phase II and III clinical trials and has demonstrated a tolerable side-effect profile and promising efficacy, showing an improved durable response rate and a trend toward superior overall survival compared to granulocyte-macrophage colony-stimulating factor. Despite these promising results, responses have been uncommon in patients with visceral metastases. T-VEC is currently being evaluated in combination with other immune therapies (ipilimumab and pembrolizumab) with early signs of activity. In this review, we discuss the preclinical rationale, the clinical experience, and future directions for T-VEC in advanced melanoma.

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“…As early as around 50 years ago, the first studies using Bacillus Calmette-Guérin were performed in oncology. In 1974, a study with 151 patients who were treated with Bacillus Calmette-Guérin was published, reporting a local response rate of 90%, a response at distant sites in 17%, and some long-lasting remissions 52. Despite some promising results, the therapy has been abandoned because of some more severe side effects and some other studies which could not confirm the initial results.…”

Section: Intralesional Immunotherapymentioning

confidence: 99%

Treating advanced melanoma: current insights and opportunities

Tronnier

Mitteldorf

2014

CMAR

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Whereas thin melanomas have an excellent prognosis after sufficient surgical treatment, melanoma disease in advanced stages is still a therapeutic challenge. After decades of frustrating studies, new therapeutic strategies have come up in the past few years. On the one hand, increasing insights into the molecular aberrations in melanoma have led to specific “targeted” therapies to affect only the mutated tumor cells, as in many other types of cancers. Today there are few “targeted” substances which are already approved and successfully used for single or combination therapy, but many others are under development. While on the other hand, nonpersonalized strategy substances have been developed successfully inducing an immunologic tumor response. Both kinds of therapy have been found to result in an improvement not only of the response rate, but also of the overall survival in metastatic disease, which represents a milestone in melanoma therapy. However, using these therapies there is still much to learn regarding the effects, the side effects, and the limitations of these promising substances.

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BCG lmmunotherapy of Malignant Melanoma

Cited by 400 publications

References 10 publications

Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA–liposome complexes

Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA–liposome complexes

Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Melanoma

Treating advanced melanoma: current insights and opportunities

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