Monitoring therapeutic response of murine tumor allografts of colon carcinoma in response to combined immunotherapy and chemotherapy (Conference Presentation)

2019 ◽  
Author(s):  
Gage J. Greening ◽  
Shelby N. Bess ◽  
Haley M. James ◽  
Ariel I. Mundo ◽  
Timothy J. Muldoon
Keyword(s):  
Colon Carcinoma ◽  
Therapeutic Response ◽  
Murine Tumor ◽  
Combined Immunotherapy

Combination of TLR9 agonist lefitolimod/MGN1703 with checkpoint inhibitors for cancer immunotherapy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 634-634 ◽  
Author(s):  
Manuel Schmidt ◽  
Kerstin Kapp ◽  
Barbara Volz ◽  
Detlef Oswald ◽  
Burghardt Wittig
Keyword(s):  
Tumor Growth ◽  
Colon Carcinoma ◽  
Checkpoint Inhibitors ◽  
Immune Surveillance ◽  
Phase Iii ◽  
Tumor Growth Inhibition ◽  
Tumor Models ◽  
Pilot Studies ◽  
Murine Tumor

634 Background: TLR9 agonists are potent activators of the immune system via induction of cellular and humoral responses. Preclinical and ongoing clinical studies support the use of TLR9 agonists for immunotherapeutic approaches. Lefitolimod/MGN1703 is a covalently-closed dumbbell-like immune surveillance reactivator (ISR) with a broad immunomodulatory potential. After promising data from a phase II trial (IMPACT) as maintenance therapy after first-line induction chemotherapy in patients with metastatic colorectal cancer lefitolimod is recently evaluated in a phase III trial in mCRC patients (IMPALA). Methods: It was previously shown that lefitolimod can reduce tumor growth in several murine tumor models. Since the mode-of-action of lefitolimod starts upstream of the initiation points of checkpoint inhibitors aCTLA-4 or aPD-1/aPD-L1 a combinatory approach may result in an enhanced anti-tumor effect. Therefore, we employed two syngeneic murine tumor models: One with s.c. inoculation of CT26 cells and another with s.c. A20 cell challenge. Multiple doses of lefitolimod were injected s.c. or i.tu. Results: In the colon carcinoma CT26 model i.p. injection of aPD-L1 had no effect on the tumor growth, whereas peritumoral injection of lefitolimod led to a slowed tumor growth. The tumor growth was further inhibited by the combination (tumor growth inhibition, TGI - aPD-L1: no, lefitolimod: 28%, combination: 48%) resulting in prolonged survival of the mice. This combinatory effect was even more pronounced in the lymphoma A20 model: Injections of anti-PD-1 (i.p.) or lefitolimod (i.tu.) alone had a moderate anti-tumor effect which was vastly increased by the combination (TGI - aPD-1: 46%, lefitolimod: 50%, combination: 99%). Conclusions: In conclusion, we showed that lefitolimod, a member of dSLIM family of TLR9 agonists and an ISR, can enhance the limited anti-tumor effects of checkpoint inhibitors in pilot studies in murine colon carcinoma and lymphoma tumor models in vivo. These data show the promising potential for the combination with checkpoint inhibitors. In fact, a clinical trial in cooperation with MD Anderson evaluating the benefit of lefitolimod in combination with ipilimumab is currently ongoing.

The influence of extracts from Rubus caesius leaves on human colon carcinoma cells cultured in vitro

Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
R Paduch ◽  
M Tomczyk ◽  
A Wiater ◽  
A Dudek ◽  
M Pleszczynska ◽  
...  
Keyword(s):  
Colon Carcinoma ◽  
Human Colon ◽  
Carcinoma Cells ◽  
Colon Carcinoma Cells ◽  
Human Colon Carcinoma ◽  
Cells Cultured

Ovarian carcinoma with bowel infiltration spread like colon carcinoma – consequences for surgical treatment

2006 ◽  
Vol 66 (S 01) ◽  
Author(s):  
A Unversucht ◽  
B Hentschel ◽  
S Hentsch ◽  
J Einenkel ◽  
LC Horn
Keyword(s):  
Surgical Treatment ◽  
Ovarian Carcinoma ◽  
Colon Carcinoma
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