Killing human lymphoma and leukemia cancer cells and TCR-activated normal human cells by dopamine D1R agonists

Abstract

The dopamine D1 / D5 receptor is highly over-expressed in various types of human and animal leukemia, lymphoma and activated T-cells. The dopamine D1 receptor is also expressed in dramatically elevated or even moderate levels in other types of cancer cells. Selective dopamine D1 receptor agonists, such as fenoldopam mesylate, rapidly, potently and selectively kill such human and animal T-cells expressing the dopamine D1 receptor. Thus, selective dopamine D1 / 5 receptor agonists may be used to treat lymphoma, leukemia and other cancers of the immune system, and T-cell mediated autoimmune diseases and other diseases caused by over-activated inflammatory T-cells (such as chronic inflammation), or graft versus host diseases (GVHD) or graft rejection, or by any other cell types expressing the dopamine D1 receptor, by killing the disease-causing cells. The selective dopamine D1 / 5 receptor agonists can be used for these purposes either in vivo or in vitro, such as to purge a given cell population from undesired leukemia, lymphoma or activated T-cells prior to further use.

Description

Background technique Lymphoma and Leukemia Humans suffer from many types of lymphomas and leukemias, which are extremely destructive tumors. In most cases, currently existing treatment modalities (chemotherapy, radiotherapy, surgery, certain other anticancer drugs, and bone marrow transplantation) are far from satisfactory, and only a relatively small proportion of lymphoma and leukemia patients survive for many years. Therefore, there is an urgent need to discover new drugs that can selectively kill lymphoma and leukemia cancer cells while affecting normal cells (non-malignant cells) much less, if at all. Dopamine and its receptors Dopamine, the most important neurotransmitter in the nervous system, has five receptors, DR1-DR5, which can be further divided into the D1R family and the D2R family. The D1R family includes D1R and D5R, and the D2R family includes D2R, D3R, and D4R. The D1 class of dopamine receptors (again, D1R and D5R belong to this class) are Gs protein...

AI Technical Summary

Problems solved by technology

Beneficial results of current treatments for all these diseases are very limited and far from satisfactory

Images