Journal of Cancer Science and Research
Open Access

Rational Combinations of Active and Passive Immunotherapy Mobilize Immune and Clinical Responses in Terminal Cancers

Chikuda Junichiro^{* *}Correspondence: Chikuda Junichiro, Department of Cancer biology and research at The University of Tokyo, Japan,

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Editorial Note

Solid tumors encroach on the hosts immune microenvironment to favor its own proliferation. Strategies to enhance the specificity of the endogenous T cell population against tumors have been met with limited clinical success. We aimed to devise a 2-tier protocol coupling in vivo whole antigen priming with ex vivo cellular expansion to clinically evaluate survival in patients following re-infusion of primed, autologous T cells, determining treatment efficacy. Treatment commenced with the acquisition of whole tumor antigens from tumor cell lines corresponding with patients primary malignancy. Lysate mixture was inoculated intradermally while Peripheral Blood Mononuclear Cells (PBMCs) were periodically extracted via phlebotomy and expanded in culture ex vivo for re-infusion. Post treatment tumor-specific T cell response and cytotoxicity was confirmed via ELI Spot and Real-Time Cell Analyzing (RTCA) Assay. Serum cytokine levels and cytotoxicity scores were evaluated for associations with survival status and duration. There was significant increase in cytotoxicity exhibited by T cells measured using both ELI Spot and RTCA following treatment. Correlation analysis determined significant association between higher post treatment cytotoxicity scores and survival status as well as longer survival duration in months. Our use of whole cell antigens proved effective in its task of in vivo priming, thereby greatly facilitating the ex vivo cell expansion as previously noted. The unique PBMC culture system used in this study achieved over 85% CD8+ lymphocyte concentration post expansion. The data showed a clear increase in tumor-specific cytotoxicity post treatment, which directly translated to an improved survival rate both categorically as well as duration in months. This same trend was backed up by the ELI Spot count which demonstrated a positive association of the ELI Spot score with survival duration. In the future, dedicated studies in the recruitment of sufficient patients of specific cancers will streamline this process and allow more in-depth analysis of post treatment changes segregated by each defined tumor cell line chosen. Conduction of formal randomized controlled trials will be the direction to take in future studies. Terminal illness or end-stage disease is a disease that cannot be cured or adequately treated and is reasonably expected to result in the death of the patient. This term is more commonly used for progressive diseases such as cancer, dementia or advanced heart disease than for injury. In popular use, it indicates a disease that will progress until death with near absolute certainty, regardless of treatment. A patient who has such an illness may be referred to as a terminal patient, terminally ill or simply as being terminal. There is no standardized life expectancy for a patient to be considered terminal, although it is generally months or less. Life expectancy for terminal patients is a rough estimate given by the physician based on previous data and does not always reflect true longevity. An illness which is lifelong but not fatal is a chronic condition.

Caregiving

Terminal patients often need a caregiver, who could be a nurse, licensed practical nurse or a family member. Caregivers can help patients receive medications to reduce pain and control symptoms of nausea or vomiting. They can also assist the individual with daily living activities and movement. Caregivers provide assistance with food and psychological support and ensure that the individual is comfortable. The patient's family may have questions and most caregivers can provide information to help ease the mind. Doctors generally do not provide estimates for fear of instilling false hopes or obliterate an individual's hope. Most caregivers become the patient's listeners and let the individual express fears and concerns without judgment. Caregivers reassure the patient and honor all advance directives. Caregivers respect the individual's need for privacy and usually hold all information confidential.