Evaluation of a Particulate Breast Cancer Vaccine Delivered via Skin

被引:30
作者
Chablani, Lipika [1 ]
Tawde, Suprita A. [2 ]
Akalkotkar, Archana [3 ]
D'Souza, Martin J. [4 ]
机构
[1] St John Fisher Coll, Dept Pharmaceut Sci, Wegmans Sch Pharm, 3690 East Ave, Rochester, NY 14618 USA
[2] Nexus Pharmaceut, Res & Dev, Vernon Hills, IL 60061 USA
[3] Charles River Labs, 1407 George Rd, Ashland, OH 44805 USA
[4] Mercer Univ, Dept Pharmaceut Sci, Coll Pharm & Hlth Sci, Vaccine Nanotechnol Lab, Atlanta, GA 30341 USA
关键词
microparticle; spray drying; whole cell lysate; microneedle; immunotherapy; LANGERHANS CELLS; DENDRITIC CELLS; IN-VITRO; TRANSCUTANEOUS IMMUNIZATION; T-CELLS; LYSATE; FORMULATION; MICROPARTICLES; MICRONEEDLES; DRUG;
D O I
10.1208/s12248-018-0285-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Breast cancer impacts female population globally and is the second most common cancer for females. With various limitations and adverse effects of current therapies, several immunotherapies are being explored. Development of an effective breast cancer vaccine can be a groundbreaking immunotherapeutic approach. Such approaches are being evaluated by several clinical trials currently. On similar lines, our research study aims to evaluate a particulate breast cancer vaccine delivered via skin. This particulate breast cancer vaccine was prepared by spray drying technique and utilized murine breast cancer whole cell lysate as a source of tumor-associated antigens. The average size of the particulate vaccine was 1.5m, which resembled the pathogenic species, thereby assisting in phagocytosis and antigen presentation leading to further activation of the immune response. The particulate vaccine was delivered via skin using commercially available metal microneedles. Methylene blue staining and confocal microscopy were used to visualize the microchannels. The results showed that microneedles created aqueous conduits of 50 +/- 10m to deliver the microparticulate vaccine to the skin layers. Further, an in vivo comparison of immune response depicted significantly higher concentration of serum IgG, IgG2a, and B and T cell (CD4+ and CD8+) populations in the vaccinated animals than the control animals (p<0.001). Upon challenge with live murine breast cancer cells, the vaccinated animals showed five times more tumor suppression than the control animals confirming the immune response activation and protection (p<0.001). This research paves a way for individualized immunotherapy following surgical tumor removal to prolong relapse episodes.
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页数:11
相关论文
共 51 条
[1]   Oral delivery of particulate prostate cancer vaccine: In vitro and in vivo evaluation [J].
Akalkotkar, Archana ;
Tawde, Suprita A. ;
Chablani, Lipika ;
D'Souza, Martin J. .
JOURNAL OF DRUG TARGETING, 2012, 20 (04) :338-346
[2]   Microneedle-mediated vaccine delivery: Harnessing cutaneous immunobiology to improve efficacy [J].
Al-Zahrani, Sharifa ;
Zaric, Marija ;
McCrudden, Cian ;
Scott, Chris ;
Kissenpfennig, Adrien ;
Donnelly, Ryan F. .
EXPERT OPINION ON DRUG DELIVERY, 2012, 9 (05) :541-550
[3]  
Ammar H. O., 2006, Current Drug Delivery, V3, P333, DOI 10.2174/156720106777731037
[4]  
Atmar RL, 2010, EXPERT REV VACCINES, V9, P1399, DOI [10.1586/erv.10.134, 10.1586/ERV.10.134]
[5]   A novel microparticulate vaccine for melanoma cancer using transdermal delivery [J].
Bhowmik, Tuhin ;
D'Souza, Bernadette ;
Shashidharamurthy, Rangaiah ;
Oettinger, Carl ;
Selvaraj, Periasamy ;
D'Souza, Martin J. .
JOURNAL OF MICROENCAPSULATION, 2011, 28 (04) :294-300
[6]   Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch microfabricated microneedles [J].
Birchall, J ;
Coulman, S ;
Pearton, M ;
Allender, C ;
Brain, K ;
Anstey, A ;
Gateley, C ;
Wilke, N ;
Morrissey, A .
JOURNAL OF DRUG TARGETING, 2005, 13 (07) :415-421
[7]   Gender variations in the optical properties of skin in murine animal models [J].
Calabro, Katherine ;
Curtis, Allison ;
Galarneau, Jean-Rene ;
Krucker, Thomas ;
Bigio, Irving J. .
JOURNAL OF BIOMEDICAL OPTICS, 2011, 16 (01)
[8]   Formulation and evaluation of a particulate oral breast cancer vaccine [J].
Chablani, Lipika ;
Tawde, Suprita A. ;
Akalkotkar, Archana ;
D'Souza, Cherilyn ;
Selvaraj, Periasamy ;
D'Souza, Martin J. .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2012, 101 (10) :3661-3671
[9]   Microfabricated silicon microneedles for nonviral cutaneous gene delivery [J].
Chabri, F ;
Bouris, K ;
Jones, T ;
Barrow, D ;
Hann, A ;
Allender, C ;
Brain, K ;
Birchall, J .
BRITISH JOURNAL OF DERMATOLOGY, 2004, 150 (05) :869-877
[10]   A Dendritic Cell Vaccine Pulsed with Autologous Hypochlorous Acid-Oxidized Ovarian Cancer Lysate Primes Effective Broad Antitumor Immunity: From Bench to Bedside [J].
Chiang, Cheryl Lai-Lai ;
Kandalaft, Lana E. ;
Tanyi, Janos ;
Hagemann, Andrea R. ;
Motz, Gregory T. ;
Svoronos, Nikolaos ;
Montone, Kathleen ;
Mantia-Smaldone, Gina M. ;
Smith, Lori ;
Nisenbaum, Harvey L. ;
Levine, Bruce L. ;
Kalos, Michael ;
Czerniecki, Brian J. ;
Torigian, Drew A. ;
Powell, Daniel J., Jr. ;
Mick, Rosemarie ;
Coukos, George .
CLINICAL CANCER RESEARCH, 2013, 19 (17) :4801-4815