Interview with Dr. Mary J. Janatpour from Dynavax Technologies
Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade.
Combination therapy generated CD8+ T cell dependent immunity leading to rejection of both non-injected and injected tumors and long-term survival, even in very large tumors.
Dr. Mary J. Janatpour from Dynavax Technologies, Inc., Emeryville, CA 94608,USA said, " It has long been appreciated by cancer researchers that the phenotypic heterogeneity and progressive evolution of malignant tumors minimizes the chance that any agent targeting a single molecular pathway could effectively cure advanced cancer . "
The authors have previously demonstrated in mouse tumor models that employing the innate immune system to prime a T cell response, in combination with checkpoint blockade, results in deep and durable anti-tumor efficacy.
These high response rates were observed in both injected and non-injected tumor lesions and patients with PD-L1 negative tumors, indicating low levels of basal immune inflammation, responded as well as patients with PD-L1 positive tumors .
Intratumorally administered SD-101 exerts its priming activity and ultimate orchestration of a systemic anti-tumor T cell response through multiple mechanisms.
The production of interferon stimulates tumor cell killing by natural killer cells, with ensuing tumor antigen release, and induces chemokines that attract T cells back to the tumor bed.
Low-dose cyclophosphamide decreases Tregs. Additional impacted biological activities have been described, such as:
- increased interferon production,
- induction of immunogenic cell death,
- increases in effector T cells, and
- increases in functional NK cells,
...likely to be complementary to SD-101 activity by virtue of modulation of the TME. By administering SD-101 locally, rather than systemically, the researchers demonstrate that localized SD-101 injection combined with systemically administered low-dose cyclophosphamide confers an anti-tumor response at non-injected sites.
The Janatpour research Team concluded that, taken together, the intratumoral SD-101 plus low-dose CY combination may complement existing checkpoint blockade therapies in patients to improve efficacy in the clinic and extend the benefits of immunotherapy to more patients.
Full text - https://doi.org/10.18632/oncotarget.27322
Correspondence to - Mary J. Janatpour - mjanatpour@dynavax.com
Keywords - TLR9, SD-101, cyclophosphamide, immune therapy, innate immunity
