The present invention relates to a human AMHRII-binding agent for its use for preventing or treating a lung cancer, and especially a non-small call lung cancer (NSCLC), and even more especially a NSCLC selected in a group comprising epidermoid NSCLC, adenocarcinoma NSCLC, large cells NSCLC and squamous cell carcinoma NSCLC and neuroendocrine NSCLC.

The improved 4-5 day, optionally 3-5 day GMP-compliant in-vitro method enables the production of macrophages from monocytes that benefits from a shorter cell culture time, fewer interventions whilst maintaining the desired characteristics of the human macrophages. The present invention describes a method wherein the monocytes are cultured in medium comprising one or more growth actors to stimulate macrophages with a pro-regenerative phenotype. The method described herein is xeno-free, serum-free and GMP compliant. In addition, further disclosed are macrophages produced according to the present invention and the use of said macrophages in the treatment of liver diseases, such as liver cirrhosis.

The improved 4-5 day, optionally 3-5 day GMP-compliant in-vitro method enables the production of macrophages from monocytes that benefits from a shorter cell culture time, fewer interventions whilst maintaining the desired characteristics of the human macrophages. The present invention describes a method wherein the monocytes are cultured in medium comprising one or more growth actors to stimulate macrophages with a pro-regenerative phenotype. The method described herein is xeno-free, serum-free and GMP compliant. In addition, further disclosed are macrophages produced according to the present invention and the use of said macrophages in the treatment of liver diseases, such as liver cirrhosis.

A method of producing helper T cells, comprising: (i) culturing T cells, which have been induced from pluripotent stem cells and into which a CD4 gene or a gene product thereof has been introduced, in a medium containing IL-2 and IL-15; and (ii) isolating CD40L-highly expressing T cells from cells obtained in step (i).

T cells, notably CD8 T cells, are known to be essential players in tumor eradication as the presence of tumor-infiltrating lymphocytes (TILS) in several cancers positively correlates with a good prognosis. To eliminate tumor cells, CD8 T cells recognize tumor antigens, which are MHC I-associated peptides present at the surface of tumor cells, with no or very low expression on normal cells. Described herein a proteogenomic approach using RNA-sequencing data from cancer and normal-matched mTEC.sup.hi samples in order to identify non-tolerogenic tumor-specific antigens derived from (i) coding and non-coding regions of the genome, (ii) non-synonymous single-base mutations or short insertion/deletions and more complex rearrangements as well as (iii) endogenous retroelements, which works regardless of the sample's mutational load or complexity.

As disclosed herein, SIRPα is integral to immuno-evasion by many different cancer types as well as cancer resistance to therapies, and reducing SIRPα levels on can bolster antigen acquisition, processing, and presentation, decrease TME immunosuppression and thereby promote tumor-specific T cell activation to eliminate tumors and generate an adaptive immune response consisting of memory T cells, circulating antibodies, and plasma cells, all of which may be specific for neo-antigens in the original cancer. Therefore, disclosed are activated SIRPα.sup.low macrophages that are useful for treating cancers.

As disclosed herein, SIRPα is integral to immuno-evasion by many different cancer types as well as cancer resistance to therapies, and reducing SIRPα levels on can bolster antigen acquisition, processing, and presentation, decrease TME immunosuppression and thereby promote tumor-specific T cell activation to eliminate tumors and generate an adaptive immune response consisting of memory T cells, circulating antibodies, and plasma cells, all of which may be specific for neo-antigens in the original cancer. Therefore, disclosed are activated SIRPα.sup.low macrophages that are useful for treating cancers.

As disclosed herein, SIRPα is integral to immuno-evasion by many different cancer types as well as cancer resistance to therapies, and reducing SIRPα levels on can bolster antigen acquisition, processing, and presentation, decrease TME immunosuppression and thereby promote tumor-specific T cell activation to eliminate tumors and generate an adaptive immune response consisting of memory T cells, circulating antibodies, and plasma cells, all of which may be specific for neo-antigens in the original cancer. Therefore, disclosed are activated SIRPα.sup.low macrophages that are useful for treating cancers.

A pharmaceutical includes helper T cells induced from pluripotent stem cells. The helper T cells include CD4-positive CD40L-highly expressing T cells, dendritic cells, antigen, and cytotoxic T cells CD8-positive T cells. The pharmaceutical can be administered in a method for treating cancer to a patient having cancer cells expressing an antigen specifically recognized by CD4-positive T cells.

The present invention relates to a method of improving the viability of macrophages subjected to cryopreservation, particularly for macrophages which are to be used in therapy, wherein the method comprises a step of maintaining the macrophages at a temperature of 2-12° C. for at least 30 minutes during either freezing or thawing procedures. Following the holding step during cooling, a cooling rate of 1 to 5° C. is used until the macrophages in a medium are frozen. For thawing the macrophages, a warming rate of 1 to 5° C. per minute is used until a temperature of 35-37° C. is reached. The present invention further relates to the cryopreserved macrophages, and the thawed macrophages produced by such methods. The technique may provide macrophages that are GMP-compliant and have a viability of at least 60%.