The construction of a lymphoma cell-based, DC-targeted vaccine, and its application in lymphoma prevention and cure

Abstract

In recent years, Non-Hodgkin lymphoma (NHL) has been one of the most fast-growing malignant tumor diseases. NHL poses severe damages to physical health and a heavy burden to patients. Traditional therapies (chemotherapy or radiotherapy) bring some benefit to patients, but have severe adverse effects and do not prevent relapse. The relevance of emerging immunotherapy options (immune-checkpoint blockers or adoptive cellular methods) for NHL remains uncertain, and more intensive evaluations are needed. In this work, inspired by the idea of vaccination to promote an immune response to destroy tumors, we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties. In this vaccine, natural tumor cells are used as a vector to load CpG-ODN, and following lethal irradiation, the formulations were decorated with mannose. The study of the characterization of the double-improved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence, which displayed an antitumor function. In the lymphoma prevention model, the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency. Furthermore, unlike the non-improved vaccine, the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model. Next, to improve the moderate therapeutic effect of the mono-treatment method, we incorporated a chemotherapeutic drug (doxorubicin, DOX) into the process of vaccination and devised a combination regimen. Fortunately, a tumor inhibition rate of ~85% was achieved via the combination therapy, which could not be achieved by mono-chemotherapy or mono-immunotherapy. In summary, the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL.

A Review on Cancer Immunotherapy and Applications of Nanotechnology to Chemoimmunotherapy of Different Cancers

“…To overcome this problem, new studies have been performed for immunotherapy alone or combined with chemotherapy by using nanotechnology. Vaccine studies are also frequently investigated in this area [ 99 , 100 ]. Notably, there are several studies with CpG, which is used as vaccine adjuvant to target lymph nodes in the literature.…”

“…For this purpose, the vaccine was combined with the anticancer drug doxorubicin. The combined system showed stronger antitumoral efficacy compared to chemotherapy and immunotherapy [ 100 ]. In another study, the efficiency of PEG-Fmoc-NLG (PEG-derivatized NLG919) micelles loaded with doxorubicin in lymphoma was investigated.…”

Biomineralized Two‐Enzyme Nanoparticles Regulate Tumor Glycometabolism Inducing Tumor Cell Pyroptosis and Robust Antitumor Immunotherapy

“…[4][5] However, the damage of chemotherapy or radiotherapy to the body is very serious. [6][7][8] As a result, a less toxic therapeutic method that can be used in combination with immunotherapy is critical. Studies have shown that regulating metabolism to treat tumors is therapy with fewer side effects and significant therapeutic effects.…”

Polysaccharide-based nanomedicines for cancer immunotherapy: A review

“…Some of these immunotherapy strategies have been adopted in clinical practices and demonstrated to be efficacious for cancer diseases. The emergence of new therapeutic targets [ 1 , 8 , 9 ] or new strategies [ [10] , [11] , [12] ] to improve the efficacy and reduce the side effect of immunotherapy are becoming attractive in cancer treatment. However, since tumor immunity is a complex process that is not fully understood yet, this emerging immunotherapy is facing great challenges such as a low targeting efficacy, which would reduce the therapeutic effect of administrated drugs, and intrinsic toxicities of immunotherapeutic drugs, which could cause severe inflammatory and autoimmune diseases [ [13] , [14] , [15] ].…”