Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Resonance enhanced multiphoton ionization photoelectron spectroscopy of gerade excited Rydberg states of the xenon dimer

Resonance enhanced multiphoton ionization with high-resolution kinetic-energy-resolved electron detection and with zero-kinetic-energy electron detection following pulsed-field ionization is performed on four excited gerade Rydberg states of the xenon dimer. Detailed information on the possible ionic cores and the dissociation limits of these states is obtained

Photoionization and photodissociation dynamics of H2 after (3+1) REMPI via the B state

We present a study of the molecular photoionization and photodissociation processes in molecular hydrogen occurring after one-photon absorption from various rovibrational levels (v = 3-22, J = 0-3) of the B 1(1sg)(2pu) state using resonance-enhanced multiphoton ionization in combination with high-resolution photoelectron spectroscopy (REMPI-PES). For one-photon absorption from the v = 3-8 levels, molecular photoionization competes with photodissociation into a ground-state atom and an atom in an n = 2 excited state. A detailed comparison of the photoelectron spectra obtained via different rotational branches and vibrational levels strongly indicates that singly excited bound 1 and 1g Rydberg states at the four-photon level exert a significant influence on the final state distributions of H. In contrast, one-photon absorption from the v = 9 and higher levels leads almost exclusively to dissociation into a ground-state atom and an excited-state atom with n > 2. Excited atomic fragments are ionized in a one-photon absorption step, and excited-atom distributions over the energetically allowed values of the principal quantum number n are obtained. Simulations of these distributions suggest that excitation of dissociative continua of bound 1(1sg)(nsg), 1(1sg)(ndg), and 1g(1sg)(ndg) Rydberg states may dominate over excitation of dissociative doubly excited 1(2pu)(npu) and 1g(2pu)(npu) states when considering the dissociation dynamics after one-photon absorption from the v9 levels of the B-state

Resonance-enhanced multiphoton ionization photoelectron spectroscopy of Rydberg states of N2O below the X ionization limit

A three-photon resonance-enhanced multiphoton ionization spectroscopic study on N2O is carried out in the spectral range from 80 000 cm - 1 up to the lowest ionization limit at 103 963 cm - 1. High-resolution photoelectron spectroscopy is used to identify and characterize the observed excited states. Eighteen origins are reported which have either not been assigned before or are reassigned now. Moreover, the photoelectron spectra taken at higher-lying resonances often show extensive vibronic coupling with the near-resonant vibronic manifolds built on lower-lying origins