NK cells exhibiting an adaptive phenotype and methods for preparing and for using

1. A method comprising culturing a population of NK cells of a blood sample from a subject in a medium to obtain a population comprising an adaptive NK cell, wherein the medium comprises:

(i-a) one or more of IL-15, IL-21, and a Notch ligand;

(ii-a) a CMV peptide-supplemented mature dendritic cell;

(iii-a) autologous monocytes and IL-15 and wherein the subject is CMV seropositive; or

(iv-a) at least one of rapamycin and an activator of CD16 signaling;

wherein the adaptive NK cell is CD56 dim and is one or more of NKG2C + and TIGIT low ;

wherein said culturing step further comprises:

(i-b) contacting the NK cells of the blood sample with an inhibitor of at least one of PLZF, TIGIT, or PD-1;

(ii-b) contacting the NK cells of the blood sample with a TIGIT inhibitor; or

(iii-b) genetically knocking down at least one of PLZF, TIGIT, or PD-1 in the NK cells of the blood sample or in the adaptive NK cell or both.

2. The method of claim 1 , wherein

(i) the TIGIT inhibitor comprises an antibody against TIGIT;

(ii) the adaptive NK cell is at least one of CD57 + , SYK − , FcεRγ − , EAT-2 − , CD45RO + , and CD45RA − ;

(iii) the adaptive NK cell exhibits reduced expression of PLZF compared to the population of NK cells prior to culture;

(iv) the adaptive NK cell exhibits an enhanced anti-tumor immune activity compared to the population of NK cells prior to culture; or

(v) the adaptive NK cell exhibits one or more of increased cytotoxicity, increased cytokine production, increased persistence, and increased resistance to T regulatory cells compared to the population of NK cells prior to culture.

3. A method comprising culturing a population of NK cells of a blood sample obtained from a subject in a medium to obtain a population comprising an adaptive NK cell, wherein the medium comprises:

(i) one or more of IL-15, IL-21, and a Notch ligand;

(ii) a CMV peptide-supplemented mature dendritic cell;

(iii) autologous monocytes and IL-15 and wherein the subject is CMV seropositive; or

(iv) at least one of rapamycin and an activator of CD16 signaling;

wherein the adaptive NK cell is CD56 dim and is one or more of NKG2C + and TIGIT low ;

wherein the method further comprising administering a cytomegalovirus (CMV) vaccine to the subject.

4. A composition comprising an enriched or isolated population of adaptive NK cells obtained by the method of claim 3 , wherein the adaptive NK cells

(i) are one or more of NKG2C + , CD57 + , and TIGIT low ;

(ii) are CD3 − and at least one of CD57 + , NKG2C + , SYK − , FcεRγ − , EAT-2 − , TIGIT low , CD45RO + , and CD45RA − ;

(iii) exhibit reduced expression of at least one of PLZF and PD-1 compared to a canonical NK cell;

(iv) are NKG2C + ;

(v) exhibit an enhanced anti-tumor immune activity compared to a canonical NK cell;

(vi) can overcome myeloid-derived suppressor cell (MDSC)-induced suppression of an immune response;

(vii) can overcome Treg-induced suppression of an immune response; or

(viii) are long-lived compared to a canonical NK cell.

5. The composition of claim 4 , wherein the composition further comprises (i) at least one of a CD155 inhibitor, a TIGIT inhibitor, and an inhibitor of the production of reactive oxygen species (ROS); and/or (ii) a pharmaceutically acceptable carrier.

6. The composition of claim 5 , wherein

(i) the inhibitor of the production of ROS comprises a catalase; or

(ii) the ROS production inhibitor or the CD155 inhibitor is present in an amount sufficient to reduce the expression of CD155 on a myeloid-derived suppressor cell (MDSC).

7. A composition comprising an enriched or isolated population of adaptive NK cells obtained by the method of claim 1 , wherein the adaptive NK cells

(i) are one or more of NKG2C + , CD57 + , and TIGIT low ;

(ii) are CD3 − and at least one of CD57 + , NKG2C + , SYK − , FcεRγ − , EAT-2 − , TIGIT low , CD45RO + , and CD45RA − ;

(iii) exhibit reduced expression of at least one of PLZF and PD-1 compared to a canonical NK cell;

(iv) are NKG2C + ;

(v) exhibit an enhanced anti-tumor immune activity compared to a canonical NK cell;

(vi) can overcome myeloid-derived suppressor cell (MDSC)-induced suppression of an immune response;

(vii) can overcome Treg-induced suppression of an immune response; or

(viii) are long-lived compared to a canonical NK cell.

8. The composition of claim 7 , wherein the composition further comprises (i) at least one of a CD155 inhibitor, a TIGIT inhibitor, and an inhibitor of the production of reactive oxygen species (ROS); and/or (ii) a pharmaceutically acceptable carrier.

9. The composition of claim 8 , wherein

(i) the inhibitor of the production of ROS comprises a catalase; or

(ii) the ROS production inhibitor or the CD155 inhibitor is present in an amount sufficient to reduce the expression of CD155 on a myeloid-derived suppressor cell (MDSC).

10. A method for treating or preventing cancer, a precancerous condition, or a virus in a subject, the method comprising administering to the subject the composition of claim 7 .

11. The method of claim 10 , wherein the subject comprises a myeloid-derived suppressor cell (MDSC).