Delivering the “Living Drug”: T Cell Immunotherapy

2022

To date nanoparticles (NPs) have been widely explored for their use in cancer. These are classified as highly efficient drug delivery systems because of their exceptional properties and design flexibility that rendered them highly targeted and safe. However, nanoparticles still face challenges regarding biological stability, non-specificity, recognition as a foreign substance, and speedy clearance that limits their applications in clinical use. To overcome these drawbacks, advanced biomimetic nanotechnology has been proposed using T-cell membrane-coated NPs as superior drug delivery systems which can increase their circulation time and prevent rapid clearance from the body by the immune system. The immune T-cells have specific surface proteins that transfer unique functionality to biomimetic NPs during the membrane extraction and coating process. Such proteins on the T-cells surface provide the nanoparticles various advantages including prolonging circulation, increasing the range of drug targets, controlled release, specified cellular interaction, and limited in vivo toxicity. In this review, T-cell membrane-based biomimetic nanosystems, their detailed extraction process, fabrication, coating over NPs, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, recent applications, future perspectives, and current challenges for their clinical translation are also presented.

APL Bioengineering

Cancer immunotherapies have revolutionized the treatment of numerous cancers, with exciting results often superior to conventional treatments, such as surgery and chemotherapy. Despite this success, limitations such as limited treatment persistence and toxic side effects remain to be addressed to further improve treatment efficacy. Biomaterials offer numerous advantages in the concentration, localization and controlled release of drugs, cancer antigens, and immune cells in order to improve the efficacy of these immunotherapies. This review summarizes and highlights the most recent advances in the use of biomaterials for immunotherapies including drug delivery and cancer vaccines, with a particular focus on biomaterials for immune cell delivery.

Artificial Cells, Nanomedicine, and Biotechnology, 2016

The cancer immunotherapy method uses the specificity of the immune system to provide a more effective than more conventional treatments, such as chemotherapy and radiotherapy. Immunotherapy has two main strategies (passive or active) to organize the immune system. Passive strategies use advantage of tumor-hyperpermeable cells, which have enhanced permeability and retention effects. Nanoparticles due to their better accumulation within tissues and cells of the immune system are well suitable for delivery of immune therapies such as vaccines or adjuvants. In this review, we explained application of nanotechnology in immunotherapy of cancer.

Oncotarget, 2016

Immunotherapies for cancer have progressed enormously over the past few decades, and hold great promise for the future. The successes of these therapies, with some patients showing durable and complete remission, demonstrate the power of harnessing the immune system to eradicate tumors. However, the effectiveness of current immunotherapies is limited by hurdles ranging from immunosuppressive strategies employed by tumors, to inadequate specificity of existing therapies, to heterogeneity of disease. Further, the vast majority of approved immunotherapies employ systemic delivery of immunomodulators or cells that make addressing some of these challenges more difficult. Natural and synthetic biomaterials - such as biocompatible polymers, self-assembled lipid particles, and implantable biodegradable devices - offer unique potential to address these hurdles by harnessing the benefits of therapeutic targeting, tissue engineering, co-delivery, controlled release, and sensing. However, despi...

Biomaterials, 2019

Cancer immunotherapy has recently burst onto the center stage of cancer treatment and research. T lymphocyte adoptive cellular transfer (ACT), a form of cancer immunotherapy, has spawned unprecedented complete remissions for terminal patients with certain leukemias and lymphomas. Unfortunately, the successes have been overshadowed by the disappointing clinical results of ACT administered to treat solid tumors, in addition to the toxicities associated with the treatment, a lack of efficacy in a significant proportion of the patient population, and cancer relapse following the treatment. Biomaterials hold the promise of addressing these shortcomings. ACT consists of two main stages-T lymphocyte ex vivo expansion followed by reinfusion into the patient-and biomaterials can improve the efficacy of ACT at both stages. In this review, we highlight recent advances in the use of biomaterials for T lymphocyte adoptive cellular cancer immunotherapy and discuss the challenges at each stage.

2021

Cancer immunotherapy has become an effective treatment in the toolbox of oncologists. Immunotherapy offers a less toxic alternative to standard cancer treatments such as chemotherapy and can have prolonged curative effects to decrease cancer recurrence. Today, many drugs and biological agents have been developed that target the immune system and elicit an antitumor/cancer response. These agents are known collectively as cancer immunotherapies. While immunotherapies have radically improved treatment outcomes for many cancer patients, there are drawbacks to using these treatments. Immunotherapy treatments have poor clinical responses in patients with tumors that lack immunogenicity. Some of the treatments also pose a risk to induce systemic toxicity when used at high doses and risks of autoimmunity are essentially inherent. To mitigate these shortcomings of immunotherapies, biomaterials can be used as a delivery vehicle to alter the pharmacokinetics, biodistribution, and control release of therapeutic agents targeting the immune system. This review article outlines the general design considerations of various biomaterials and their applications in cancer immunomodulation. Many studies show promising results in murine tumor models with potential for translation to human disease, but further research-via rigorous clinical trials-is needed to assess the effectiveness of immunomodulatory biomaterials in cancer patients. VI

Pharmaceutics, 2021

Cancer, a group of diseases responsible for the second largest cause of global death, is considered one of the main public health problems today. Despite the advances, there are still difficulties in the development of more efficient cancer therapies and fewer adverse effects for the patients. In this context, nanobiotechnology, a materials science on a nanometric scale specified for biology, has been developing and acquiring prominence for the synthesis of nanocarriers that provide a wide surface area in relation to volume, better drug delivery, and a maximization of therapeutic efficiency. Among these carriers, the ones that stand out are those focused on the activation of the immune system. The literature demonstrates the importance of this system for anticancer therapy, given that the best treatment for this disease also activates the immune system to recognize, track, and destroy all remaining tumor cells.

Immunotherapy holds tremendous promise for improving cancer treatment in which an appropriate stimulator may naturally trigger the immune system to control cancer. Up-to-date, adoptive T-cell therapy has received two new FDA approvals that provide great hope for some cancer patient groups. Nevertheless, expense and safety-related issues require further study to obtain insight into targets for efficient immunotherapy. The development of material science was largely responsible for providing a promising horizon to strengthen immunoengineering. In this review, we focus on T-cell characteristics in the context of the immune system against cancer and discuss several approaches of exploiting engineered particles to manipulate the responses of T cells and the tumour microenvironment.

Accounts of Chemical Research, 2020

Metrics & More Article Recommendations CONSPECTUS: Therapeutic manipulation of the immune system against cancer has revolutionized the treatment of several advanced-stage tumors. While many have benefited from these treatments, the proportion of patients responding to immunotherapies is still low. Nanomedicines have promise to revolutionize tumor treatments through spatiotemporal control of drug activity. Such control of drug function could allow enhanced therapeutic actions of immunotherapies and reduced side effects. However, only a handful of formulations have been able to reach human clinical studies so far, and even fewer systems are being used in the clinic. Among translatable formulations, self-assembled nanomedicines have shown unique and versatile features for dealing with the heterogeneity and malignancy of tumors in the clinic. Such nanomedicines can be designed to promote antitumor immune responses through a series of immunopotentiating functions after being directly injected into tumors, or achieving selective tumor accumulation upon intravenous administration. Thus, tumor-targeted nanomedicines can enhance antitumor immunity by several mechanisms, such as inducing immunogenic damage to cancer cells, altering the tumor immune microenvironment by delivering immunomodulators, or eliminating or reprogramming immunosuppressive cells, enhancing the exposure of tumorassociated antigens to antigen presenting cells, stimulating innate immunity mechanisms, and facilitating the infiltration of antitumor immune cells and their interaction with cancer cells. Moreover, nanomedicines can be engineered to sense intratumoral stimuli for activating specific immune responses or installed with ligands for increasing drug levels in tumors, granting subcellular delivery, and triggering immune signals and proliferation of immune cells. Thus, the ability of nanomedicines to exert immunomodulatory functions selectively in tumor and tumor-associated tissues, such as draining lymph nodes, increases the efficiency of the treatments, while avoiding systemic immunosuppressive toxicities and the exacerbation of adverse immune responses. Moreover, the compartmentalized structure of self-assembled nanomedicines offers the possibility to coload a variety of drugs for controlled pharmacokinetics, enhanced tumor delivery, and synergistic therapeutic output. Also, by integrating imaging functionalities into nanomedicines, it is possible to develop theranostic platforms reporting the immune settings of tumors as well as the effects of nanomedicines on the tumor immune microenvironment. Herein, we critically reviewed significant strategies for developing nanomedicines capable of potentiating antitumor immune responses by surmounting biological barriers and modulating antitumor immune signals. Moreover, the potential of these nanomedicines for developing innovative anticancer treatments by targeting particular cells is discussed. Finally, we present our perspectives on the awaiting challenges and future directions of nanomedicines in the age of immunotherapy.

Cancers

In the last few decades, cancer immunotherapy becomes an important tactic for cancer treatment. However, some immunotherapy shows certain limitations including poor therapeutic targeting and unwanted side effects that hinder its use in clinics. Recently, several researchers are exploring an alternative methodology to overcome the above limitations. One of the emerging tracks in this field area is nano-immunotherapy which has gone through rapid progress and revealed considerable potentials to solve limitations related to immunotherapy. Targeted and stimuli-sensitive biocompatible nanoparticles (NPs) can be synthesized to deliver immunotherapeutic agents in their native conformations to the site of interest to enhance their antitumor activity and to enhance the survival rate of cancer patients. In this review, we have discussed cancer immunotherapy and the application of NPs in cancer immunotherapy, as a carrier of immunotherapeutic agents and as a direct immunomodulator.