Novel nanobiologic trains immunity, curbs tumor growth in mice

Reuters Health - 02/11/2020 - A bone marrow-targeted nanobiologic, MTP(10)-HDL, induced trained immunity and potentiated checkpoint inhibition in a mouse melanoma model, suggesting the approach could eventually be used as anti-cancer therapy, researchers say.

"Our current estimate is to reach human trials between two and four years from now," Dr. Willem Mulder of Eindhoven University of Technology in The Netherlands and the Icahn School of Medicine at Mount Sinai in New York City told Reuters Health by email.

"Manufacturing is, of course, a critical hurdle, and we have developed a process that is scalable and good manufacturing practice-compatible," he said. "Thereafter, pharmacokinetic and toxicity studies should advance the program to an Investigational New Drug Application."

As reported in Cell, Dr. Mulder and colleagues delivered MTP-HDL intravenously to mice with melanoma. The resulting induction of trained immunity led to myelopoiesis, the production of trained myeloid cells in the bone marrow.

The trained myeloid cells changed the tumor microenvironment, allowing immune cells to effectively combat the melanoma cells. In an additional experiment, the nanobiologic displayed similar characteristics in non-human primates, with a favorable safety profile.

Summing up, the authors conclude that MTP-HDL favorably accumulates in hematopoietic organs of mice and non-human primates; induces trained immunity through bone marrow progenitors in vivo; inhibits tumor growth; and potentiates immune checkpoint inhibition.

Taken together, they say, the findings suggest that this approach could be used as a stand-alone anti-cancer therapy or in conjunction with checkpoint inhibitor drugs.

Dr. Mulder added, "We are working on the versatility of our approach by conducting studies in different cancer models including, but not limited to, pancreatic, breast, and lung,"

Dr. Wasif Saif, deputy physician-in-chief and medical director at the Northwell Health Cancer Institute in Lake Success, New York, called the approach "promising."

"This approach seems very relevant in patients who are being treated with a checkpoint inhibitor," he said. "It is also (possible) that this approach can be used as an anti-cancer treatment as monotherapy as well, but it needs validation in longitudinal studies."

"It can also aid us to develop radiopharmaceutical imaging, such as PET scans, to better visualize biodistribution of a promoter drug within bone marrow, spleen and blood of a patient affected by trained immunity," he added.

An important limitation, he said, "is that this approach was studied in a mouse melanoma model, a tumor type which is generally immunogenic. Therefore, trained immunity has to be investigated in less immunogenic cancer types. Moreover, long-term studies of the duration of anticancer benefit, plus epigenetic and immunological profiles, are warranted, as indicated by the authors."

"In the years ahead, we expect these trained-immunity-targeted therapeutics will not be limited to treating only cancer, but can be employed to treat other conditions, such as inflammatory and autoimmune disorders, allergies, cardiovascular disease and certain infections," he concluded.

Dr. Mulder and four coauthors are co-founders and have equity in Trained Therapeutix Discovery in the Grand Duchy of Luxembourg, a biotech company that is developing the nanobiologic.

By Marilynn Larkin

SOURCE: https://bit.ly/3erTI8k Cell, online October 29, 2020.



Posted on 2 November 202020 November 2020