Truncated car peptides and methods and compositions using truncated car peptides

Abstract

Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences, such as truncated CAR peptides, that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of PCT Application No. PCT / US2011 / 026535, filed Feb. 28, 2011, which claims benefit of U.S. Provisional Application Ser. No. 61 / 308,826, filed Feb. 26, 2010. PCT / US2011 / 026535, filed Feb. 28, 2011, and U.S. Provisional Application Ser. No. 61 / 308,826, filed Feb. 26, 2010, are hereby incorporated herein by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH[0002]This invention was made with government support under grant 1 R41 HL088771 from the National Heart Lung Blood Institute (NHLBI) of the National Institutes of Health (NIH). The government has certain rights in the invention.REFERENCE TO SEQUENCE LISTING[0003]The Sequence Listing submitted Sep. 1, 2011, as a text file named “SBMRI—57—8401_AMD_AFD_Sequence_Lisiting_Text_File.txt,” created on Sep. 1, 2011, and having a size of 37,865 bytes is hereby incorporated by reference pursuant to 37 C.F.R. §1.52(e)(5).FIELD OF T...

AI Technical Summary

Benefits of technology

[0031]In some forms, the tCAR composition can have a therapeutic effect. In some forms, the co-composition or cargo composition can have a therapeutic effect. In some forms, the therapeutic effect can be a slowing in the increase of or a reduction of tumor burden. In some forms, the therapeutic effect can be a slowing of the increase of or reduction of tumor size. In some forms, the therapeutic effect can comprise a reduction in inflammation, an increase in speed of wound healing, reduction in amounts of scar tissue, decrease in pain, decrease in swelling, or decrease in necrosis. In some forms, the therapeutic effect can comprise pulmonary vasodilation, decrease in pulmonary pressure, anti-coagulation, airway smooth muscle relaxation, increase in glutathione (GSH), decrease in inflammatory immune response, inhibition of thromboxane synthesis, or inhibition of leukotriene synthesis.

[0040]In some forms, the tCAR composition can have a therapeutic effect. In some forms, the co-composition or cargo composition can have a therapeutic effect. In some forms, the therapeutic effect can be a slowing in the increase of or a reduction of tumor burden. In some forms, the therapeutic effect can be a slowing of the increase of or reduction of tumor size. In some forms, the therapeutic effect can comprise a reduction in inflammation, an increase in speed of wound healing, reduction in amounts of scar tissue, decrease in pain, decrease in swelling, or decrease in necrosis. In some forms, the therapeutic effect can comprise pulmonary vasodilation, decrease in pulmonary pressure, anti-coagulation, airway smooth muscle relaxation, increase in glutathione (GSH), decrease in inflammatory immune response, inhibition of thromboxane synthesis, or inhibition of leukotriene synthesis.

Problems solved by technology

A major limitation of these peptides as delivery vehicles is that they are not selective; they enter into all cells.

Tissue penetration is a serious limitation in the delivery of compositions to cells.

The frequently cited “leakiness” of tumor vessels does not appear to substantially mitigate this problem.

Tissue injuries caused by trauma, medical procedures, and inflammation are a major medical problem.

Systemic medication is available for most major medical conditions, but therapeutic options in promoting tissue regeneration are largely limited to local intervention.

A major problem limiting tissue regeneration is scar formation.

A major hurdle to advances in treating cancer is the relative lack of agents that can selectively target the cancer while sparing normal tissue.

For example, radiation therapy and surgery, which generally are localized treatments, can cause substantial damage to normal tissue in the treatment field, resulting in scarring and loss of normal tissue.

Chemotherapy, in comparison, which generally is administered systemically, can cause substantial damage to organs such as the bone marrow, mucosae, skin and small intestine, which undergo rapid cell turnover and continuous cell division.

As a result, undesirable side effects such as nausea, loss of hair and drop in blood cell count often occur when a cancer patient is treated intravenously with a chemotherapeutic drug.

Such undesirable side effects can limit the amount of a drug that can be safely administered, thereby hampering survival rate and impacting the quality of patient life.

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