The present invention relates to an isolated cellular targeted delivery system comprising a CD45+ leukocyte cell comprising within said cell a complex of one or more iron binding proteins and/or a label as well as methods for producing such isolated cellular targeted delivery system and uses of such system for therapy diagnosis and in particular for diagnosis of cancer, particularly metastatic cancer, in particular for therapy of cancer.

Provided herein are mertansine polypeptide conjugates useful in the treatment of cancer, pharmaceutical compositions comprising the same, and methods of use and preparation thereof. The methods provided herein are highly N-terminal selective and are capable of yielding N-terminal mertansine conjugated polypeptides with site selectivity of 99% or greater.

Provided herein are hemoglobin-based therapeutic agents useful for treating cancer, pharmaceutical composition including the same, and methods of use and preparation thereof.

Provided herein are mertansine polypeptide conjugates useful in the treatment of cancer, pharmaceutical compositions comprising the same, and methods of use and preparation thereof. The methods provided herein are highly N-terminal selective and are capable of yielding N-terminal mertansine conjugated polypeptides with site selectivity of 99% or greater.

Compositions and methods for improving transperitoneal oxygen uptake during peritoneal ventilation for extrapulmonary oxygenation of an organism or individual organs in preferably life-threatening case of need, such as pulmonary failure or circulatory shock, are disclosed. Such deficiencies can be addressed by transperitoneal administration of oxygen via a gas introduced into the abdominal cavity. A liquid, preferably aqueous, composition including an oxygen carrier such as hemoglobin is used, which, surprisingly, is capable of increasing the effectiveness of the diffusion of the oxygen administered by a one-time or repeated filling or continuous flushing of the abdominal cavity. An oxygen carrier, such as hemoglobin or derivatives thereof, is used for the manufacture of a composition for improvement of the diffusion of oxygen (gas) introduced into mucus layers of the peritoneum, preferably to enhance the diffusion of oxygen in transperitoneal ventilation.

The beta 2 subunit of mouse hemoglobin (HBB2) has been identified as soluble factor from mouse lungs that exhibits cytostatic/cytotoxic activity against neuroblastoma lung micrometastases. The beta subunit of human hemoglobin (HBB) has been found to have similar activity. Methods of using these proteins and fragments thereof in the treatment of cancer and inhibition of metastasis are provided, along with methods of screening a subject for micrometastases by detecting HBB in a biological sample.

The present invention relates to an isolated cellular targeted delivery system comprising a CD45.sup.+ leukocyte cell comprising within said cell a complex of one or more iron binding proteins and an active ingredient as well as methods for producing such isolated cellular targeted delivery system and uses of such system for therapy, in particular for therapy of cancer.

The present invention relates to an isolated cellular targeted delivery system comprising a CD45+ leukocyte cell comprising within said cell a complex of one or more iron binding proteins and/or a label as well as methods for producing such isolated cellular targeted delivery system and uses of such system for therapy diagnosis and in particular for diagnosis of cancer, particularly metastatic cancer, in particular for therapy of cancer.

The invention provides methods, compositions, and medical kits comprising a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders and preservation of blood products. In one aspect, the invention provides methods, compositions, and medical kits comprising an inorganic nitrite salt and a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders, such as cancer, cardiovascular disorders, ischemic conditions, hemolytic conditions, and bacterial infections. Exemplary inorganic nitrite salts include sodium nitrite and arginine nitrite. Exemplary allosteric modulators of hemoglobin described herein include alkyl-substituted and acyl-substituted di-nitroheterocycles.

The disclosure concerns a class of hemoglobin based oxygen carriers (HBOCs) comprising a first hemoglobin protein cross-linked by a chemical reaction that is followed by a strain-promoted alkyne-azide cycloaddition (SPAAC) reaction or by a strain-promoted alkyne-nitrone cycloaddition (SPANC) in the absence of added copper salts to a second modified cross-linked hemoglobin protein. The resulting construct is an HBOC that is capable of binding oxygen and releasing same in a useful manner upon addition in an appropriate solution to the circulatory system of a patient. The disclosure also concerns a method of production of the HBOC where a first and second hemoglobin protein are produced by covalently linking hemoglobin to an angle strained cycloalkyne moiety. A compound comprising at least 2 azide or nitrone moieties is then added for reacting under conditions conducive to SPAAC or SPANC in reaction in absence of copper ions with the first and second hemoglobin protein for causing covalent linkage of the first and second hemoglobin protein to the compound comprising said at least 2 azide or nitrone moieties, resulting in said HBOC. The HBOC can be used for transfusion, perfusion or for increasing oxygen transport.