We have developed a family of monoclonal antibodies that have the same specificity based on a binding, complementarity determining region (“CDR”) sequence homology. Our lead product is a humanized monoclonal antibody (our “mAb” or “SIWA 318H”). It targets a SIWA-identified, naturally-occurring cell surface marker (our “SIWA Marker”) on both cancer cells and senescent cells (“SCs”), which cells are thereby destroyed and removed through normal processes. Our family of antibodies includes SIWA 318M, a murine homolog that we used in our early in vitro and in vivo studies.
SIWA has conducted several in vivo preclinical studies. which have shown that using SIWA 318 over a short period of time has been able to statistically significantly:
- Reduce senescent cells as measured by p16INK4a
- Increase muscle mass in a naturally aged mouse model
- Inhibit metastatic lung foci in a 4T1 breast cancer model
Across these studies, no adverse effects from SIWA 318 were recorded.
Pilot study to test SIWA318H in a humanized mouse xenograft model for pancreatic cancer
The pancreatic tumor cell line PSN1 generated consistently measurable tumors in all CD34+ NSG mice injected. These tumors were easy to measure and were proven to be an adequate tumor model to evaluate biological effect of SIWA318H. Ten days after tumor implantation mice were treated with either isotype control or SIWA318H. Results show that tumors in mice treated with SIWA318H grew significantly slower than those in mice treated with isotype control antibody (p<0.001) (Figure 1).
Muscle Wasting Pre-Clinical Data
A study using a murine version of SIWA 318 in naturally-aged CD-1 mice achieved a statistically significant reduction in senescent cells, as measured by a reduction in p16INK4a. As expected, the reduction in senescent cells was coupled with a statistically significant increase in muscle mass, as measured in the gastrocnemius muscle, back to a level comparable to young mice controls. Study results were achieved with 3 weeks of twice daily injection of SIWA 318. Treated mice showed no adverse effects of treatment and no regression was observed in the post-treatment, 9-week treatment free period. The charts below show some of these results.
GREEN ■ designates old mice at 2.5µg per gram
PURPLE ■ designates old mice at 5µg per gram
BLUE ■ designates young mice controls
RED ■ designates old mice controls
Cancer Metastasis Results
A preclinical study showed that removal of senescent cells using a murine form of SIWA 318 significantly inhibited tumor metastasis. Importantly, there were no observable adverse effects from the treatment and no increase in tumor growth over the control group.
The study was done in a BALBc 4T1 metastatic breast cancer mouse model. Mice were grouped to receive 5 ug/g, 10 ug/g, or saline injections two times daily for three weeks. A fourth group received no treatment. When the study ended at 23 days, the 10ug/g group showed 30% (p < 0.001) fewer metastatic lung foci compared to the control group.
Some Images of 318H Binding Results