Yale University

Columbia University

Francis P Gasparro

Richard L Edelson

Lawrence I Deckelbaum

Robert E Tigelaar

Charles Cantor

Wilma A Saffran

Bauer K Sumpio

Bauer E Sumpio

John T Welsh

Methods and pharmaceutical compositions for modifying the immune response of a mammal to a specific antigen are provided. The methods include treating an antigen presenting cell to enhance expression of a major histocompatibility complex molecule and reacting the treated antigen presenting cell with the antigen extracorporeally to form an antigen-associated antigen presenting cell.

Specific immune system modulation

Methods and pharmaceutical compositions for improving the effectiveness of radiation therapy for treating a subject having an internal solid tumor malignancy are disclosed. The methods include irradiating the tumor to release tumor-derived antigens in vivo, preparing a cellular vaccine including the isolated antigens admixed with a preparation of altered antigen presenting cells and administering the cellular vaccine to the subject. In the preferred embodiments, the antigen presenting cells are leukocytes that have been photochemically altered by subjecting the cells to photopheresis.

Methods and compositions for improving the effectiveness of

A method for inhibiting smooth muscle cell proliferation in an injured blood vessel includes the steps of administering a photoactivatable psoralen to a patient in an amount to achieve local arterial tissue levels of psoralen suitable for light-dependent inhibition of smooth muscle cell growth, and delivering radiation in the visible wavelength range to the injured region of the blood vessel at a level sufficient for photoactivation of the psoralen. The psoralen is preferably 8-methoxypsoralen and can be delivered systemically or locally. The method of the invention can be used for preventing restenosis in a blood vessel following transluminal angioplasty. Both the psoralen and the visible light can be delivered with a laser balloon catheter having a porous balloon. The method of the invention may also be used for inhibiting proliferation of other undesired cell types in a patient's body.

Inhibition of smooth muscle cell proliferation by 8-methoxypsoralen

Methods and pharmaceutical compositions for modifying the immune response of a mammal are provided. The pharmaceutical compositions include a pharmaceutically acceptable carrier and a plurality of cells containing psoralen-DNA monoadducts and substantially no psoralen-DNA crosslinks. The preparation is formed by irradiating a suspension of cells with visible light radiation in the presence of psoralen.

Immune system modulation using psoralens activated with visible light

A method of inhibiting the function of targeted DNA in a viable cell comprising administering to a viable cell containing targeted DNA a therapeutically effective amount of a photoactivatable composition comprising the UVA irradiation product of a compound that has two photoactivatable functional groups, and an oligonucleotide of DNA whose sequence of bases (a) contains at least one TA or AT sequence and (b) is substantially complementary to a segment of cellular DNA of the targeted DNA in the cell, and irradiating the cell with UVA light.

Selective inhibition of gene expression by photoactivatable

The present invention provides a compound having the formula ##STR1## wherein Y is biotin or iminobiotin, X is CH.sub.2, P is psoralen or a psoralen derivative, r is an integer equal to or greater than 2 and s is an integer equal to or greater than 1. The invention also provides a method for preparing a biotinylated psoralen or a biotinylated psoralen derivative. Further provided are methods for detecting, purifying, and isolating nucleic acids, and methods for delivering an iminobiotinylated psoralen to a cell.

Growing community of inventors

Hamden, CT, United States of America

Francis P Gasparro