A Systemic Complete Response of Metastatic Melanoma to Local Radiation and Immunotherapy

BACKGROUND: Melanoma is a relatively immunogenic tumor, in which infiltration of melanoma cells by T lymphocytes is associated with a better clinical prognosis. We hypothesized that radiation-induced cell death may provide additional stimulation of an anti-tumor immune response in the setting of anti-CTLA-4 treatment. METHODS: In a pilot melanoma patient, we prospectively tested this hypothesis. We treated the patient with two cycles of ipilimumab, followed by stereotactic ablative radiotherapy to two of seven hepatic metastases, and two additional cycles of ipilimumab. RESULTS: Subsequent positron emission tomography-computed tomography scan indicated that all metastases, including unirradiated liver lesions and an unirradiated axillary lesion, had completely resolved, consistent with a complete response by RECIST. CONCLUSION: The use of radiotherapy in combination with targeted immunotherapy as a noninvasive in vivo tumor vaccine strategy appears to be a promising method of enhancing the induction of systemic immune responses and anti-tumor effect.     

On the influence of local molecular environment on the redox potential of electron transfer cofactors in bacterial photosynthetic reaction centers

The addition of cryosolvents (glycerol, dimethylsulfoxide) to a water solution containing bacterial photosynthetic reaction centers changes the redox potential of the bacteriochlorophyll dimer but does not affect the redox potential of the quinone primary acceptor. It is shown that the change in redox potential can be due to variation of the electrostatic interactions between cofactors and the local molecular environment, which is modified by solvent additives. The degree of influence of a solvent on the redox potential of various cofactors is determined by their solvent accessibility, i.e. on their arrangement in the structure of reaction centers.     

Photodynamic therapy for multiple skin cancers

Photodynamic therapy is a new treatment modality under trial in a number of centers for use in both early and late tumors of the aerodigestive tract, bladder, brain, and skin. The theory behind its application relies on the selective uptake by a tumor bed of a photosensitizing agent such as hematoporphyrin derivative (HPD) and subsequent exposure of the tumor-bearing area to coherent laser light of suitable frequency. Following exposure, necrosis of tumor occurs to a variable degree depending on the amount of sensitizing agent absorbed by the tumor, the wavelength of laser light applied, the depth of penetration of light into the tumor, and the quantum of light energy delivered. Lack of controlled clinical data on the use of photodynamic therapy in multiple cancers of the skin led us to perform a pilot clinical study in patients. The results of this study were poor enough for us to abandon, on ethical grounds, a planned full clinical trial of the modality. The results are presented and possible reasons for failure of the method are discussed.     

CB 1954 (2,4-dinitro-5-aziridinyl benzamide) becomes a DNA interstrand crosslinking agent in Walker tumour cells

Walker tumour cells were shown to be uniquely sensitive to CB 1954 when compared with other cells in vitro. CB 1954 forms DNA-DNA interstrand crosslinks in a time-dependent manner in Walker tumour but not Chinese hamster cells. The absence of interstrand crosslinks in hamster cells was not due to a lack of uptake of drug but rather to a failure to convert (probably by bioreduction) CB 1954 to the required reactive difunctional intermediate.