Methods of enhancing or modifying nk cells

The method of any preceding claim, wherein the enriching comprises contacting the population of cells with a substrate displaying anti-CD3 antibodies or anti-CD3 fragments thereof and retaining cells bound by said substrate.

The method of any preceding claim, wherein the enriching comprises contacting the population of cells with magnetic beads displaying anti-CD3 antibodies or anti-CD3 fragments thereof and using magnetism to retain cells bound by said beads.

A method for enhancing one or more functions of a population of cells comprising TCR-NK cells, the method comprising:

• obtaining a population of cells comprising TCR-NK cells;
• and
• contacting the population of cells with an agent capable of binding to CD3.

The method of any preceding claim, wherein the population of cells comprising TCR-NK cells is obtained by:

• culturing a population comprising NK cells under activating conditions;
• and
• transducing the activated NK cells under conditions to transfer at least one exogenous nucleic acid to the NK cells, wherein the one or more exogenous nucleic acids encode a TCR and/or one or more CD3 chains.

The method of any preceding claim, wherein the population of cells is cultured under expansion conditions after being enriched and/or enhanced.

The method of any preceding claim, wherein the enriched/enhanced population is suitable for therapeutic infusion.

The method of any preceding claim, wherein the method further comprises cryopreserving the enriched/enhanced population and/or formulating the enriched/enhanced population into a pharmaceutical composition.

A method of producing natural killer (NK) cells that comprise one or more exogenous nucleic acids encoding a TCR or portion thereof, the method comprising:

• i) culturing NK cells under activating conditions;
• and
• ii) transducing the activated NK cells under conditions to transfer the one or more exogenous nucleic acids to the NK cells, wherein the transduction takes place on the 4th day or later day after the beginning of step i).

A population comprising TCR-NK cells for use in a method of treatment, wherein, prior to administration, the TCR-NK cells are contacted in vitro with an anti-CD3 agent.