Randomized clinical study on intratumoral BCG-cell wall preparation (CWP) therapy in patients with squamous cell carcinoma in the head and neck region

Bier, J.; Rapp, Herbert J.; Borsos, Tibor; Zbar, B.; Kleinschuster, Stephen J.; Wagner, H. N.; Röllinghoff, Martin

doi:10.1007/bf00200315

Cited by 19 publications

(3 citation statements)

References 41 publications

(39 reference statements)

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“…Later, accumulating pre-clinical evidence supported the use of BCG for cancer therapy (16). Clinicians reported the therapeutic benefits of intra-tumoral injections of BCG in several types of cancers such as melanoma (17–20) or squamous cell carcinoma of the head and neck (21). MD Anderson hospital reported up to 2500 patients with all types of cancer treated with BCG, including scarification of the tumors (22).…”

Section: Introductionmentioning

confidence: 99%

Intratumoral Immunization: A New Paradigm for Cancer Therapy

Marabelle

Kohrt

Caux

et al. 2014

Clinical Cancer Research

189

143

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Immune cell infiltration in the tumor microenvironment is of prognostic and therapeutic import. These immune cell subsets can be heterogeneous and are composed of mature antigen presenting cells, helper and effector cytotoxic T cells, toleragenic dendritic cells, tumor associated macrophages, and regulatory T-cells, among other cell types. With the development of novel drugs that target the immune system rather than the cancer cells, the tumor-immune microenvironment is not only prognostic for overall patient outcome, but also predictive for likelihood of response to these immune-targeted therapies. Such therapies aim to reverse the cancer immunotolerance and trigger an effective anti-tumor immune response. Two major families of immunostimulatory drugs are currently in clinical development: pattern recognition receptor agonists (PRRagos) and immunostimulatory monoclonal antibodies (ISmAbs). Despite their immune targeted design, these agents have so far been developed clinically as if they were typical anti-cancer drugs. Here, we review the limitations of this conventional approach, specifically addressing the shortcomings of the usual schedules of intravenous infusions every two or three weeks. If the new modalities of immunotherapy target specific immune cells within the tumor microenvironment it might be preferable to deliver them locally into the tumor rather than systemically. There is pre-clinical and clinical evidence that a therapeutic systemic anti-tumor immune response can be generated upon intra-tumoral immunomodulation. Moreover, pre-clinical results have shown that therapeutic synergy can be obtained by combining PRRagos and ISmAbs to the local tumor site.

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Section: Introductionmentioning

confidence: 99%

Intratumoral Immunization: A New Paradigm for Cancer Therapy

Marabelle

Kohrt

Caux

et al. 2014

Clinical Cancer Research

189

143

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“…In the last two decades immunotherapy with Bacillus Calmette-Gu6rin (BCG) has been widely studied in experimental animal tumour systems [3,27], in spontaneously occurring tumours in pet [30] and farm animals [18,23,24] and in tumours in man [4,15,40]. In horses intralesional immunotherapy with BCG was used by Wyman et al [47] and Murphy et al [29] for the treatment of sarcoid skin tumours in 2 and 7 horses respectively.…”

Section: Introductionmentioning

confidence: 99%

Equine sarcoid: BCG immunotherapy compared to cryosurgery in a prospective randomised clinical trial

Misdorp

et al. 1986

Cancer Immunol Immunother

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A total of 30 horses with single or multiple sarcoid tumors of the skin were randomly divided into three treatment groups: (i) cryosurgical treatment, (ii) intralesional immunotherapy with a live BCG vaccine, (iii) intralesional immunotherapy with a BCG cell wall preparation. Complete tumour regression was obtained in all 10 cryosurgically treated horses, in 6 of 10 live BCG treated horses, and in 7 of 10 BCG cell wall treated horses. One live BCG and 2 BCG cell wall treated horses showed partial tumour regression of more than 50% of the tumour area. Eleven horses with sarcoid tumours were not eligible for random allocation in the trial because unfavourable site or size of the tumour precluded cryosurgical treatment. These animals were treated with BCG cell wall vaccine except for 1 animal, which was treated with live BCG. In 4 cases this treatment was combined with cytoreductive surgery of the tumour. In this prognostically unfavourable group 8 animals showed complete tumour regression and 3 animals did not respond. Regression after BCG immunotherapy appeared to correlate with size (larger tumours worse response) and localization of the sarcoid (less favourable results in the limb), and increase in peripheral blood leucocytes after the first injection. Horses with a positive delayed type hypersensitivity reaction to PPD before the start of treatment showed a tendency to more favourable prognosis than PPD negative horses. No correlation was present between regression and single or multiple presence of sarcoids, increase in body temperature after injection of BCG and the formation of specific antibodies to BCG. None of the cured animals have shown tumour recurrence 3 to 40 months following treatment.

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“…When the dosage of BCG increased to 5 mg/ml, a marked increase of NK cell activity was demonstrated Discussion BCG is a nonspecific biological response modifier and has been used systemically as an immunotherapeutic agent in many malignant diseases without satisfactory results [19]. However, it did have favorable responses in treating certain malignancies such as melanoma [20], squamous cell carcinoma of head and neck [21 ], and blad der tumor [22][23][24][25]. Intravesical instillation of BCG for Table 1.…”

Section: Resultsmentioning

confidence: 99%