Methods for using bioadhesive and steric interactions of copolymers with at least two moieties to minimize adverse effects mediated by external influences on cell, tissue, organ system, and organism biology
Methods for using bioadhesive and stearic interactions specific to copolymers with at least two moieties, to minimize adverse effects mediated by external influences on cell, tissue, organ system, and organism biology. Copolymers have bioadhesive properties driven by electrostatic and hydrophobic interactions and passivation though hydrophilic moieties. These copolymers are useful for reducing rates of viral infectivity in target cells, and in reducing host morbidity. These copolymers are useful for reducing ADC related toxicity including corneal epithelial toxicity. Formulations of these copolymers are safe and well tolerated. Epithelial cells and surfaces including precursor or stem cell corneal epithelial cells are treated with these copolymers to confer utility and benefit.
1 . A method to decrease an ocular adverse event(s) in a patient undergoing antibody-drug conjugate therapy, where said adverse event(s) comprise damage to nonneoplastic cells, the method comprising
applying to said patient a copolymer in an amount and a time effective to decrease said damage or adverse effects to said nonneoplastic cells,
wherein said copolymer is poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG),
wherein said step of applying said copolymer to said patient decreases said damage or adverse effects to said nonneoplastic cells,
wherein said ocular adverse event is corneal epithelial toxicity associated with antibody-drug conjugate therapy, and
and wherein said copolymer is applied to corneal and conjunctival epithelial cells of said patient in an amount and a time effective to decrease corneal epithelial toxicity associated with said antibody-drug conjugate therapy in said patient.
2 . The method of claim 1 , wherein said copolymer is applied to corneal epithelial cells at risk of antibody-drug conjugate (ADC) uptake.
3 . The method of claim 1 , wherein said step of applying said copolymer to said patient is prior to initiation of systemic antibody-drug conjugate therapy in said patient.
4 . The method of claim 1 , wherein said step of applying said copolymer to said patient is after initiation of systemic antibody-drug conjugate therapy in said patient, wherein applying said copolymer decreases symptoms of ocular adverse events associated with the antibody-drug conjugate therapy in said patient.
5 . The method of claim 1 , wherein said copolymer is applied to the eye of said patient, optionally as an eye drop formulation, in an amount and for a time effective to reduce the number of dose holds and dose reductions of antibody-drug conjugates in the treatment of human malignancy, thereby reducing corneal adverse events and ocular safety concerns, in an at-risk patient.
6 . A method to decrease an ocular adverse event(s) in a patient undergoing monoclonal antibody therapy, wherein said adverse event(s) comprise damage to the corneal epithelium, said method comprising:
applying a copolymer to said patient in an amount and for a time effective to decrease said damage or adverse effects to the corneal epithelium,
wherein said copolymer is poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG),
wherein said ocular adverse event(s) is corneal epithelial toxicity associated with monoclonal antibody therapy,
wherein said step of applying said copolymer to said patient decreases said damage to the corneal epithelium,
wherein said copolymer is applied to corneal and conjunctival epithelial cells of said patient in an amount and for a time effective to decrease said corneal epithelial toxicity associated with monoclonal antibody epithelial toxicity in said patient.
7 . The method of claim 1 , where said decrease in adverse events comprising damage to nonneoplastic cells is a numerical reduction in the adverse events comprising damage to nonneoplastic cells in said patient compared with untreated comparative patients.
8 . The method of claim 7 , where said numerical reduction is at least 5% compared with untreated comparative populations.
9 . The method of claim 6 , where said decrease in corneal epithelial toxicity is a numerical reduction in the corneal epithelial toxicity in said patient compared with untreated comparative patients.
10 . The method of claim 9 , where said numerical reduction is at least 5% compared with untreated comparative populations.