# Nano-Therapeutic Approaches for Oncogenic Herpesvirus-Mediated Malignancies

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $743,574

## Abstract

Two types of human gamma-herpesviruses, Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated
herpesvirus (KSHV) are linked to variety of lymphoproliferative and neoplastic disorders. KSHV infection is known
to associate with Kaposi’s sarcoma (KS), oral-KS, primary effusion lymphoma (PEL; or body-cavity B-lymphoma),
as well as a subset of multicentric Castleman’s disease. EBV is etiologically associated with Burkett’s lymphoma,
nasopharyngeal carcinoma, both Hodgkin's and non-Hodgkin's lymphomas, T/NK cell lymphoma, and post-
transplant lymphoproliferative disorder. PEL is one of the most aggressive forms of non-Hodgkin’s lymphoma.
Current chemotherapeutic approaches, unfortunately, result in dismal outcomes with a short median survival of less
than 10 months. Although its incidence is relatively rare, we think development of new therapeutic approaches is
still important. Furthermore, successful therapeutic approaches developed for PEL should be applicable to other
oncogenic herpesvirus-mediated cancer types.
 Current chemotherapeutic agents can effectively eradicate cancer cells but efficacy is limited by “off-target
effects” leading to considerable toxicity. In addition, the majority of patients with lymphoma are elderly and
effectiveness is limited by co-morbid conditions that include renal, liver or cardiac dysfunction. If we could manipulate
the drugs so that the drugs primarily accumulate in the tumors while simultaneously decreasing the “off-target effects”,
we can increase the effectiveness of the drugs and decrease side-effects; this will ultimately improve efficacy.
 In this application, we are developing new therapeutic approaches with Nano capsules by utilizing FDA-
approved porphyrin as a material. By encapsulating cancer drugs in our nanoparticles, we could increase the
applicable dose of chemotherapy drugs from 3 to 8-fold in mouse and even 20-fold in rat studies. This is very
important for a number of reasons; (1) we may be able to revive very effective but toxic anti-cancer drugs that
previously failed to obtain FDA approval due to off-target effects. (2) We may also increase the dose level of
currently used anti-cancer drugs without increasing side effects. (3) Most importantly, our invention may enable
physicians to treat patients who did not have an option for chemotherapy due to co-morbid conditions. Finally, by
applying our knowledge in herpesvirology, we robustly reactivate latently infected virus from naturally-infected
cancer cells with a combination of cancer drugs. By doing this, the infected virus starts to replicate in the cancer
cells and eventually kills the tumor cells. Cancer cells but not healthy normal cells are infected by the virus, thus we
can selectively kill cancer cells by using already infected herpesvirus. By careful selection of the cancer drugs, we
inhibit the completion of viral replication thereof infection to neighboring normal cells. By using the combination of
nanotechnology with oncolytic stra...

## Key facts

- **NIH application ID:** 9949673
- **Project number:** 5R01CA232845-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Yoshihiro Izumiya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $743,574
- **Award type:** 5
- **Project period:** 2018-07-06 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949673

## Citation

> US National Institutes of Health, RePORTER application 9949673, Nano-Therapeutic Approaches for Oncogenic Herpesvirus-Mediated Malignancies (5R01CA232845-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9949673. Licensed CC0.

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