Intralesional interferon therapy for basal cell carcinoma

Cornell, Roger C.; Greenway, Hubert T.; Tucker, Stephen B.; Edwards, Libby; Ashworth, Susan; Vance, J. Corwin; Tanner, Daniel J.; Taylor, Eugene L.; Smiles, Kenneth A.; Peets, Edwin A.

doi:10.1016/0190-9622(90)70276-n

Cited by 190 publications

(87 citation statements)

References 24 publications

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“…To address this need, we have begun to develop methods to enhance gene expression in a disease model where local protein production has provided clinical efficacy. 3,9 Recombinant IFN-␣ has been used with some success in BCC, but is often limited by the need to repeat injections required to sustain durable remissions. In this study, we have analyzed the potential of gene delivery to provide for more sustained IFN production locally.…”

Section: Discussionmentioning

confidence: 99%

“…3,9 To analyze the effects of recombinant IFN gene expression, cDNAs encoding human IFN subtypes ␣2, ␣4, ␣7, ⍀1, and mouse IFN ␣2 and ␣7 were prepared by RT-PCR from peripheral blood mononuclear cells (PBMC) and inserted into the same CMV-regulated eukaryotic expression vector. These plasmids were transiently transfected into human melanoma cells, which are not responsive to IFN, and supernatants were analyzed for their biological activity with an interferon-responsive element (IRE) reporter, IRE-CAT, in Jurkat T-leukemia cells.…”

Section: Biological Activity Of Different Interferon Subtypes In Vitromentioning

confidence: 99%

“…Results from several clinical trials indicate that interferon can be effective in the treatment of basal cell carcinoma. [2][3][4][5][6][7][8] Multiple intralesional injections of IFN-␣2 over a 3-week period induced overall remission rates of 70 to 100%. 3,9 Increased numbers of CD4 + T cells surrounding the BCC infiltrating tumor island in the dermis have been observed after intralesional IFN-␣ therapy.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5][6][7][8] Multiple intralesional injections of IFN-␣2 over a 3-week period induced overall remission rates of 70 to 100%. 3,9 Increased numbers of CD4 + T cells surrounding the BCC infiltrating tumor island in the dermis have been observed after intralesional IFN-␣ therapy. [10][11][12] It has also been shown previously that the number of antigenpresenting cells (APC) expressing HLA-DR and CD1a is reduced in BCC, compared with normal human skin.…”

Section: Introductionmentioning

confidence: 99%

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Liposome-mediated gene transfer into human basal cell carcinoma

et al. 1999

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Section: Discussionmentioning

confidence: 99%

Section: Biological Activity Of Different Interferon Subtypes In Vitromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Liposome-mediated gene transfer into human basal cell carcinoma

et al. 1999

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“…The prominence of the host inflammatory response around resolving tumors suggests a role for the immune response in eliminating the tumor (6). Finally, intralesional administration ofcytokines, such as IL-2, IFN--y, and IFN-a, can induce resolution of these tumors (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Local expression of antiinflammatory cytokines in cancer.

Yamamura

Modlin²,

Ohmen³

et al. 1993

J. Clin. Invest.

172

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To characterize the nature of the local cytokine response to cancer, we chose to investigate cytokine patterns in biopsy specimens of basal cell carcinoma (BCC). We hypothesized that a distinct pattern of local cytokine production may be characteristic of BCC, a neoplasia of epidermis, in comparison to the pattern of seborrheic keratosis (SK), a benign growth of epidermis. We analyzed cytokine mRNAs in BCC versus SK by performing polymerase chain reaction on mRNA derived from biopsy specimens. The mRNAs encoding cytokines for IL4, IL-5, IL-10, and granulocyte macrophage colony-stimulating factor were strongly expressed in BCC lesions and weakly expressed in SK lesions. Conversely, IL-2, IFN-,y, and lymphotoxin mRNAs were strongly expressed in SK lesions and weakly expressed in BCC lesions. The response to malignancy, BCC, was typified by cytokines characteristic of murine TH2 cells. This cytokine pattern favors humoral immunity with concomitant immunosuppression of cell-mediated immune responses. In comparison, the response to the benign growth, SK, was typified by cytokines characteristic of murine THi cells that favor cell-mediated immune reactions. The findings of a distinct cytokine pattern in skin cancer provide a framework to develop strategies for immunologic intervention. (J. Clin. Invest. 1993Invest. . 91:1005Invest. -1010

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Interferon

Greenway

Cornell²

1990

Arch Dermatol

Self Cite

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and Lindenmann1 has led to the establishment of a new field of research involving virology, immunology, tumor destruction, cell biology, and molecular genetics, as well as other disciplines. The bearers of interference (interferons) constitute a class of glycoproteins exhibiting antitumor, antiviral, and immu-See also p 1029. nologic properties. Three types of interferons are currently recognized: interferon alfa (alpha leukocyte interferon), interferon beta (fibroblast interferon), and interferon gamma (immune interferon). All three types of interferon have specific structures with interferon alfa and beta being most closely related. Multiple subtypes exist for interferon alfa and several for interferon beta.In this issue of the Archives, Edwards and coworkers2 demonstrate the antitumor effect of interferon alfa-2b in a sustained release formulation for the treatment of basal cell carcinomas. Two treatment regimens were utilized: a single injection of 10 million IU and a similar regimen (10 million IU) given once per week for 3 weeks. Both nodular and superficial basal cell carcinomas were included. Cure rates were 52% with those patients treated with one injection, and 80% for those patients receiving three injections. Two patients discontinued injections be¬ cause of side effects, with 82% of the patients experi¬ encing at least one severe adverse reaction.Interferon alfa has been shown to provide a safe and effective treatment for superficial and nodular basal cell carcinoma.3 Our initial study utilized a reg-imen of 1.5 million IU injected intralesionally three times a week for 3 weeks (nine total injections). All eight of the initial patients were completely cured with histologie excision of the treatment site found to exhibit no evidence of residual basal cell carcinoma.Minimal side effects were observed and were easily controlled with the administration of oral acetamin¬ ophen.Various studies have been conducted at our insti¬ tution and others in an effort to achieve the optimum dose. It was found that the administration of smaller doses over a shorter period of time resulted in decreased tumor response and cure rates. Increasing the dosage over shorter periods of time was also ac¬ companied by increased side effects. A large, multicenter trial for the evaluation of intralesional therapy of nodular and superficial basal cell carcinomas with the original treatment regimen of 1.5 million IU three times a week for 3 weeks is currently in press,4 with over an 80% cure rate achieved in this double-blind study with a 1-year histologie evaluation period.Other types of interferon appear to have much less effect than does interferon alfa in the treatment of basal cell carcinoma. Tank and coworkers4 and Ed¬ wards and coworkers6 both revealed a decreased an¬ titumor response in the intralesional treatment of basal cell carcinoma with interferon gamma, as com¬ pared with interferon alfa. Thus, it appears that the type of interferon appears to be significantly impor¬ tant in the treatment of basal cell carcinoma.The c...

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Intralesional interferon therapy for basal cell carcinoma

Cited by 190 publications

References 24 publications

Liposome-mediated gene transfer into human basal cell carcinoma

Liposome-mediated gene transfer into human basal cell carcinoma

Local expression of antiinflammatory cytokines in cancer.

Interferon

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