Researchers cite using Cellero primary mouse spleen cells in an independent publication focused on evaluating anti-tumor immunity. [1]

It is well-established in the scientific community that tumor cells use immune suppression as a way of evading the body’s immune response, thus allowing cancer to grow and spread.  Scientists have developed several strategies for dealing with this hurdle to more effective cancer therapy, but so far, there is no universally effective solution.

Mouse models are essential in cancer research, providing knowledge on underlying mechanisms and cellular pathways and acting as valuable intermediate therapeutic models on the way to clinical development.  In a recent study, New York-based scientists (Martomo et al., 2021) used a series of murine cancer cell lines, and mouse primary spleen cells to evaluate the efficacy of a novel fusion protein designed to block immune suppression while prolonging the immune response. [1]

The fusion protein the lab created is called KD033, and it is designed with a dual function in mind. Part of the protein blocks PD-L1, an inhibitory receptor expressed on some tumor cells that suppresses the immune response by reducing T-cell activity. The other part of the fusion protein contains the active domain of IL-15, a cytokine that stimulates immune cell proliferation. [2] The group synthesized a human/monkey version of the fusion protein (KD033), along with a human/monkey/murine version (srKD033), and a non-targeting version of the peptide (ntKD033) that would be used for separating out the two mechanisms of action.

Since the researchers wanted to screen the new fusion peptide against cancer cell types present in various tissues, they obtained a panel of mouse cancer cell lines representing cancer of the skin, liver, colon, prostate, bladder, breast, and lung tissue.  The group also obtained cryopreserved primary mouse spleen cells from Cellero to carry out IL-15-induced proliferation studies.

Cellero carries a large selection of mouse primary immune cells for preclinical research. Each immune cell type is available in a 5-10 million cell/vial format and characterized through screening for the presence of cell type-specific surface markers via flow cytometry.

In preliminary studies, mouse spleen cell proliferation increased in direct correlation to increasing doses of every fusion peptide containing the IL-15 sequence, but not when exposed to increasing doses of the anti-PD-L1 fragment alone. (Fig. 1)

For their mouse tumor models, mice were inoculated with the various murine cancer cell lines and then treated with srKD033. A single dose of the fusion peptide showed robust anti-tumor effects and increased survival time in multiple mouse models.  The peptide was 100% effective in the colorectal cancer model, inducing complete remission of tumor growth.

Cell surface markers for both the innate and adaptive immune response were significantly increased by administration of srKD033, as measured by flow cytometry. The fusion peptide also produced a durable memory response, a result the scientists attributed to the capacity to target the effects of IL-15 to the tumor microenvironment.

Overall, the KD033 fusion peptide series showed high efficacy against tumors in a mouse model, with a good safety profile after repeated doses and a durable response. These results certainly warrant further development toward clinical testing.

Cellero is committed to providing top-quality starting materials for your clinical and pre-clinical studies. The mouse splenocytes in this study were supplied cryopreserved; for best results with our cryopreserved products, we recommend using Cellero’s approved thawing protocol.

 

Reference:

  1. Martomo S. A., et al. Single-Dose Anti–PD-L1/IL-15 Fusion Protein KD033 Generates Synergistic Antitumor Immunity with Robust Tumor-Immune Gene Signatures and Memory Responses. Molecular Cancer Therapeutics. 20:347–56. 2021.
  2. Robinson T. O., and Schluns K. S. The potential and promise of IL-15 in immuno-oncogenic therapies. Immunology Letters. 190: 159-168. Oct 2017.

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