Enhancing cancer chemo-immunotherapy by biomimetic nanogel with tumor targeting capacity and rapid drug-releasing in tumor microenvironment

In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel (NG@M) to co-deliver chemotherapeutic paclitaxel (PTX) and immunotherapeutic agent interleukin-2 (IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA-co-HP-β-cyclodextrin-co-Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ, followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate (39 days).

Mathematical Model of Colorectal Cancer with Monoclonal Antibody Treatments.

We present a new mathematical model of colorectal cancer growth and its response to monoclonalantibody (mAb) therapy. Although promising, most mAb drugs are still in trial phases, and the possible variations in the dosing schedules of those currently approved for use have not yet been thoroughly explored. To investigate the effectiveness of current mAb treatment schedules, and to test hypothetical treatment strategies, we have created a system of nonlinear ordinary differential equations (ODEs) to model colorectal cancer growth and treatment. The model includes tumor cells, elements of the host’s immune response, and treatments. Model treatments include the chemotherapy agent irinotecan and one of two monoclonal antibodies - cetuximab, which is FDAapproved for colorectal cancer, and panitumumab, which is still being evaluated in clinical trials. The model incorporates patient-specific parameters to account for individual variations in immune system strength and in medication efficacy against the tumor. We have simulated outcomes for groups of virtual patients on treatment protocols for which clinical trial data are available, using a range of biologically reasonable patient-specific parameter values. Our results closely match clinical trial results for these protocols. We also simulated experimental dosing schedules, and have found new schedules which, in our simulations, reduce tumor size more effectively than current treatment schedules. Additionally, we examined the system’s equilibria and sensitivity to parameter values. In the absence of treatment, tumor evolution is most affected by the intrinsic tumor growth rate and carrying capacity. When treatment is introduced, tumor growth is most affected by drugspecific PK/PD parameters.

Appication of chemo- immunotherapy using M. Vaccae for newly diagnosed pulmonary tuberculosis AFB (+) in Ha Tay and Ha Noi

Background: \r\n', u'In the antituberculosis chemotherapy, shortening treatment course, and applying new high effective methods are top prioritized. Of which,the immunotherapy with M vaccea an environmental saprophyte, combined with the antituberculosis medicines all over the world has been applied since 1985, aimed to enhance the host immune responses.\r\n', u'Objectives:\r\n', u'To evaluate the results after 6 months of shortened course anittuberculosis chemotherapy by combining the immunotherapy withM vaccae.\r\n', u'Subjects and method: \r\n', u'233 newly diagnosed pulmonary tuberculosis patients with AFB smear (+) selected from Centers for Tuberculosis Control in some districts of Ha Tay and Ha Noi. They are 15 above, and not the pregnant, breastfeeding, diabetes, HIV infections, and hepatitis B (Unnecessary) \r\n', u'Dividing randomly into 2 groups, group A was in treatment of the standard 8 month chemotherapy regimen, and group B was treated in a shortned 6 month chemotherapy regimen in combination with immunotherapy by using M. vaccae vaccine. \r\n', u'Results:\r\n', u'The rates of AFB (-) sputum of group B were 98,2% and 100% respectively, the rates of the group A were 97,4% and 99% respectively after 2 and 6 months of treatment. There are 88.5% and 100% for group B, 85.6% and 98.8% for group A at the same time to achieve a negative sputum culture for M. tuberculosis. IgM responses against M. tuberculosis sonicated antigen before and after the follow-up time in Group A are not changed, whereas this level of the immunotherapy group had reduced significantly at the 6th moth (P<0.05). There is no responses in IgC to M. tuberculosis of both groups during the same follow-up period. The mean weight of patients in group B was higher than that of group A after 2 and 6 months of treatment.\r\n', u'Conclusion:\r\n', u'M. vaccae vaccine brings good benefits when be combined with the chemo-immunotherapy for newly diagnosed pulmonary tuberculosis patients with AFB smear (+). The negative sputum indicators and clinic improvements in the chemo- immunotherapy group of treatment are better than that of chemotherapy only. This study created more effective method for treating tuberculosis infection.\r\n', u'

The Treatment of Moderately Advanced Carcinoma with Chemo-Immunotherapy / 中国肿瘤生物治疗杂志

A comparison of effectiveness of chemo-immunotherapy (CIT) using LAK/CD3AK 1-2 weeks after TACE in 74 patients with no surgical indication and TACE alone in 41 patients with moderately advanced HCC was carried out. The rates of remission between CIT group and TACE alone group were 72.4% and 40.4%(P