Photodynamic therapy‐generated tumor cell lysates with CpG‐oligodeoxynucleotide enhance immunotherapy efficacy in human papillomavirus 16 (E6/E7) immortalized tumor cells

Bae, Seog Nyeon; Kim, Yong‐Wan; Kwak, Sun-Young; Kim, Yong-Wook; Ro, Duck-Yeong; Shin, Jong-Chul; Park, Choong-Hak; Han, Soo Jeong; Oh, Chung-Hun; Kim, Chong‐Kook; Ahn, Woong‐Shick

doi:10.1111/j.1349-7006.2007.00447.x

Cited by 33 publications

(29 citation statements)

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“…In this way, it is similar to thermal and cryotherapies (43 -45). It has been shown that HSP70 released from PDT-treated cells has a key role in immune induction (6,8) perhaps via activation of dendritic cells (42). PDT-induced cell lysates have been shown to be much more active than freeze/thaw tumor cell lysates in generating an antitumor response, and they contain much more HSP70 (8).…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that HSP70 released from PDT-treated cells has a key role in immune induction (6,8) perhaps via activation of dendritic cells (42). PDT-induced cell lysates have been shown to be much more active than freeze/thaw tumor cell lysates in generating an antitumor response, and they contain much more HSP70 (8). A recent article by Kabingu et al (7) has shown that PDT control of distant (untreated) tumors required a competent immune system, required natural killer cell activity, and led to persistent CD8 + T-cell-mediated cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Amplification for specific products was then carried out using the SybrGreener kit from Invitrogen on a Corbette 3000 real-time PCR instrument. The majority of primers were designed using the Primer3 Web interface 8 and were synthesized by Integrated DNA Technologies. Commercial, verified primers for apoptotic markers were also obtained from Sigma and verified primers for h-actin were obtained from Real-time Primers.…”

Section: Translational Relevancementioning

confidence: 99%

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New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

Starkey¹,

Rebane

Drobizhev³

et al. 2008

Clinical Cancer Research

228

189

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Purpose: The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation on normal tissues and characterized the response of xenograft tumors to our PDT protocols. Experimental Design: Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon activated PDT. Results:Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal, changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation. Conclusions: These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was consistent with known responses to singlephoton activated PDT. Experiments in larger animals are warranted to determine the maximal achievable depth of treatment.Photodynamic therapy (PDT; ref. 1) is a protocol that uses light of the appropriate wavelength to activate photosensitizer accumulated in tumor tissue to its triplet state (2). The triplet excitation energy can be effectively transferred to molecular oxygen, resulting in the generation of singlet oxygen, superoxide radical, and other active oxygen species (2, 3). The singlet oxygen causes direct chemical damage to tumor and/or tumor endothelial cells (4), initiates a neutrophilic inflammatory response (5), and can stimulate both innate and specific antitumor immune responses (6 -8). Singlet-oxygen production, however, requires a sufficiently high energy of the triplet state of the sensitizer. Long-wavelength near-IR (NIR) light k ex > 750 nm has relatively low-photon energy, which restricts the range of processes that can be activated by one-photon excitation. The relation between the wavelength and the minimum excitation energy of singlet oxygen is shown in Fig. 1A. The dark gray shaded area corresponds to the excitation energy below the required minimum value, E so < 1.5 -1.6 eV (9, 10), which shows that sensitization by one-photon absorption (1PA) fails in the phototherapeutic window 780 to 950 nm, where tissues have maximum transparency to light. Sensitization by simultaneous two-photon absorption (2PA; ref. 11) combines the energy of two photons and can provide suffi...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Translational Relevancementioning

confidence: 99%

See 1 more Smart Citation

New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

Starkey¹,

Rebane

Drobizhev³

et al. 2008

Clinical Cancer Research

228

189

View full text Add to dashboard Cite

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“…PDT-cell lysates coinjected with CpG showed significant suppression of tumor growth in mice at both prophylactic and therapeutic levels as compared with each treatment alone and appeared to be mediated by CD81 T cells. 108 These data suggest that PDT-cell lysates along with CpG may be another possible strategy for HPV immunotherapy.…”

Section: Photodynamic Therapymentioning

confidence: 89%

Recent advances in strategies for immunotherapy of human papillomavirus‐induced lesions

Kanodia

Silva

Kast

2007

Intl Journal of Cancer

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Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for ''proof of concept'' studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in preclinical models for HPVinduced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; immunotherapy; therapeutic vaccines; immunomodulation; animal models; clinical trialsThe human papillomaviruses (HPVs) are a family of sexually transmitted, double-stranded DNA viruses with over 100 different genotypes identified till date. HPV genotypes are divided into the low-risk and high-risk categories based on the spectrum of lesions they induce. Fifteen HPV types are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82); 3 are classified as probable high-risk types (26, 53 and 66) and 12 are classified as low-risk types (6,11,40,42,43,44,54,61,70,72, 81 and CP6108). 1 The low-risk types primarily induce benign genital condylomas and low-grade squamous intraepithelial lesions whereas the high-risk types are most frequently associated with the development of anogenital cancers and can be detected in 99% of cervical cancers, 2 with HPV16 found in about 50% of cases. 3 Infection by the low-risk types is not confined to the anogenital area and can cause other diseases such as recurrent respiratory papillomatosis. Similarly, infection by the high-risk types is also not confined to the anogenital area, since 18.3% of cancers of the oropharynx contain DNA from these types. 4 In the United States, an estimated 75% of the sexually active general population ages 15-49 years acquires at least one genital HPV type during their lifetime. 5 Though most individuals remain asymptomatic and spontaneously clear their infections, a small percentage of patients develop clinically or histologically recognizable lesions that develop into invasive cancer. The widespread use of cervical cytological screening using Papanicolaou (Pap) smear tests has reduced the mortality rate from cervical cancer in developed countries. However, in developing countries where screening programs are minimal, cervical cancer remains the second leading cause of cancer-related deaths among women. 6 Furthermore, Pap smear tests will not help identify HPV infection in males, where it can cause penile and anal cancers as well as cancers of the head and neck. Thus, it is essential to develop effective prophylactic and therapeutic strategies directed against HPV. Prophylactic vaccinesWhile therapeutic vaccines aim to develop a strong ...

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“…The use of novel photosensitizers such as Bremachlorin may help to resolve this issue. Combination treatments of PDT and immunotherapy to improve the therapeutic effect are being investigated preclinically and clinically using nonspecific immunostimulatory agents (43)(44)(45). However, tumor-specific immunotherapy such as therapeutic peptide vaccination with HPV antigens may be preferred to ensure a stronger and target-specific effect.…”

Section: Discussionmentioning

confidence: 99%

Combination of Photodynamic Therapy and Specific Immunotherapy Efficiently Eradicates Established Tumors

Kleinovink

Driel

Snoeks

et al. 2016

Clinical Cancer Research

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Purpose: The efficacy of immunotherapy against advanced cancer may be improved by combination strategies. Photodynamic therapy (PDT) is a local tumor ablation method based on localized activation of a photosensitizer, leading to oxygen radical-induced tumor cell death. PDT can enhance antitumor immune responses by release of antigen and danger signals, supporting combination protocols of PDT with immunotherapy.Experimental Design: We investigated the local and systemic immune effects of PDT after treatment of established tumors. In two independent aggressive mouse tumor models, TC-1 and RMA, we combined PDT with therapeutic vaccination using synthetic long peptides (SLP) containing epitopes from tumor antigens.Results: PDT of established tumors using the photosensitizer Bremachlorin resulted in significant delay of tumor outgrowth. Combination treatment of PDT with therapeutic SLP vaccination cured one third of mice. Importantly, all cured mice were fully protected against subsequent tumor rechallenge, and combination treatment of primary tumors led to eradication of distant secondary tumors, indicating the induction of a systemic antitumor immune response. Indeed, PDT by itself induced a significant CD8 þ T-cell response against the tumor, which was increased when combined with SLP vaccination and essential for the therapeutic effect of combination therapy. Conclusions:We show that immunotherapy can be efficiently combined with PDT to eradicate established tumors, based on strong local tumor ablation and the induction of a robust systemic immune response. These results suggest combination of active immunotherapy with tumor ablation by PDT as a feasible novel treatment strategy for advanced cancer.

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Photodynamic therapy‐generated tumor cell lysates with CpG‐oligodeoxynucleotide enhance immunotherapy efficacy in human papillomavirus 16 (E6/E7) immortalized tumor cells

Cited by 33 publications

References 40 publications

New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

Recent advances in strategies for immunotherapy of human papillomavirus‐induced lesions

Combination of Photodynamic Therapy and Specific Immunotherapy Efficiently Eradicates Established Tumors

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